The study developed a mild method to prepare partially reduced graphene oxide(pRGO).Through the non-covalent interaction of pRGO with nucleic acid aptamers AS1411 and indocytinine green(ICG),photothermal and photosens...The study developed a mild method to prepare partially reduced graphene oxide(pRGO).Through the non-covalent interaction of pRGO with nucleic acid aptamers AS1411 and indocytinine green(ICG),photothermal and photosensitive nanocomposites pRGO-AS1411-ICG(pRAI)were constructed.The complex structure and morphological characteristics of pRGO and pRAI were used by fourier transform infrared spectroscopy(FTIR),raman spectroscopy(Raman),X-ray photoelectron spectroscopy(XPS),ultraviolet-visible spectroscopy(Uv-vis),and transmission electron microscope(TEM).And the effect of EDS phototherapeutic back heat therapy on tumor cells was carried out in cell experiments.The results showed that pRAI with targeting of AS1411 can effectively kill tumor cells through the dual effects of photothermal therapy(PTT)and photodynamic therapy(PDT).展开更多
Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumo...Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.展开更多
Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor ther...Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.展开更多
AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic sear...AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTSThree RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study.CONCLUSIONIVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.展开更多
Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparati...Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.展开更多
AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizuma...AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.展开更多
Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performanc...Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performance of photothermalconversion limits the therapeutic effect of combination therapy. In this study, two-dimensional boron (boron, B) nanoparticles wereprepared by ultrasonic exfoliation, and copper sulfide (CuS) nanoparticles and doxorubicin (DOX) were grown on the surface ofthe nanoparticles to form B-CuS-DOX nanoparticles. B-CuS carrier has high DOX drug loading capacity (864mg/g) and goodphotothermal conversion performance (photothermal conversion efficiency at 808nm is 55.8%). At the same time, it can achievedrug release and good photothermal response at near infrared and pH. The nanoparticles designed in this study are expected toprovide an effective chemotherapy-photothermal therapy strategy for tumor therapy in vivo.展开更多
Introducing heavy halogen atoms into organic small molecules is a practical strategy for efficient singlet oxygen(^(1)O_(2))generation.Generally,bromine or iodine atoms are introduced on the aza-borondipyrromethene(az...Introducing heavy halogen atoms into organic small molecules is a practical strategy for efficient singlet oxygen(^(1)O_(2))generation.Generally,bromine or iodine atoms are introduced on the aza-borondipyrromethene(aza-BODIPY)core,rather than on the periphery aryl rings for efficient~1O_(2) generation.Herein,an aza-BODIPY dye NBDPBr with unexpected bromination on the periphery aryl rings was synthesized for photoacoustic(PA)imaging-guided synergistic photothermal therapy(PTT)and photodynamic therapy(PDT)in tumor cells.Owing to unexcepted bromination at the periphery aryl rings,NBDPBr demonstrated an outstanding singlet oxygen quantum yield(Φ_(Δ))of 66% which was superior to similar brominated photosensitizers previously reported.After encapsulation with amphiphilic polymer F-127,hydrophilic NBDPBr nanoparticles(NPs)were fabricated and exhibited an excellent photothermal conversion efficiency(η)of 43.0% under 660 nm photoirradiation.In vivo PA imaging results demonstrated that NBDPBr NPs could specifically accumulate at tumor sites and realized the maximum tumor retention at 7 h post-injection.All the in vitro and in vivo results indicated the significant potence of NBDPBr with unexpected bis-bromination for PA imaging-guided synergetic PDT/PTT.展开更多
Multimodal treatment modalities hold great potential for cancer therapy,thus current efforts are focusing on the development of more effective and practical synergistic therapeutic platforms.Herein,we present a novel ...Multimodal treatment modalities hold great potential for cancer therapy,thus current efforts are focusing on the development of more effective and practical synergistic therapeutic platforms.Herein,we present a novel trans,trans,trans-[Pt(N_(3))_(2)(OH)_(2)(py)_(2)](Pt(Ⅳ))prodrug-initiated hydrogel microparticles(M_(ICG-Pt))with indocyanine green(ICG)encapsulation by microfluidics for efficiently synergistic chemo-,photothermal(PTT)and photodynamic therapy(PDT).The employed Pt(Ⅳ)could not only serves as an initiator to generate azidyl radical(N_(3)^(·))for photo-polymerization of methacrylate gelatin(GelMA)matrix,but also be reduced to high cytotoxic platinum(Ⅱ)(Pt(Ⅱ))species for tumor chemotherapy.The laden ICG with highly photothermal heating ability and intrinsic reactive oxygen species(ROS)productivity endows the M_(ICG-Pt) with effective PTT/PDT performances upon near-infrared(NIR)light irradiation.In addition,benefiting from the production of oxygen during the photo-activation process of Pt(Ⅳ),the PDT efficacy of ICG-laden M_(ICG-Pt) could be further enhanced.Based on these advantages,we have demonstrated that the M_(ICG-Pt) could significantly eliminate cancer cells in vitro,and remarkably suppressed the tumor growth in vivo via synergistic chemotherapy,PTT,and PDT.These results indicate that such Pt(Ⅳ)-initiated hydrogel microparticles are ideal candidates of multimodal treatment platforms,holding great prospects for cancer therapy.展开更多
Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operati...Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to targettumors. Selective therapies can be established by focusing on distinctive intracellular(receptors, apoptotic pathways, multidrug resistance system, nitric oxidemediated stress) and environmental(glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity.展开更多
Aurum nanomaterials(ANM), combining the features of nanotechnology and metal elements, have demonstrated enormous potential and aroused great attention on biomedical applications over the past few decades. Particularl...Aurum nanomaterials(ANM), combining the features of nanotechnology and metal elements, have demonstrated enormous potential and aroused great attention on biomedical applications over the past few decades. Particularly, their advantages, such as controllable particle size, flexible surface modification, higher drug loading, good stability and biocompatibility, especially unique optical properties, promote the development of ANM in biomedical field. In this review, we will discuss the advanced preparation process of ANM and summarize their recent applications as well as their prospects in diagnosis and therapy. Besides, multi-functional ANM-based theranostic nanosystems will be introduced in details, including radiotherapy(RT), photothermal therapy(PTT), photodynamic therapy(PDT), immunotherapy(IT), and so on.展开更多
Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable ...Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic.Yet,it suffers from certain limitations during clinical exploitation,including insufficient photosensitizers(PSs)delivery,tumor-oxygenation dependency,and treatment escape of aggressive tumors.To overcome these obstacles,an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles(NPs)by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers.Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation.A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment.This review provides an overview of available data regarding the design,methodology,and oncological outcome of the innovative NPs-based PDT of PCa.展开更多
Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other c...Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other conditions.PDT not only provide a precise and selective method for the treatment of various diseases by itself,it can also be used in combination with other traditional therapies.Because PDT uses light as the unique targeting mechanism,it has simpler and more direct targeting capability than traditional therapies.The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances.Different photosensitizers have their distinct characteristics,leading to different advantages and disadvantages.These could be enhanced or compensated by using proper PDT system.Therefore,the selected type of photosensitizer would heavily influence the overall design of a PDT system.In this article,we evaluated major types of inorganic and organic PDT photosensitizers,and discussed future research directions in the field.展开更多
Therapeutic failures are always accompanied by surgery,chemotherapy,and radiotherapy when metastasis or therapeutic resistance is present in tumors.Thus,it is of critical importance to optimize the therapeutic strateg...Therapeutic failures are always accompanied by surgery,chemotherapy,and radiotherapy when metastasis or therapeutic resistance is present in tumors.Thus,it is of critical importance to optimize the therapeutic strategy to realize a high curative effect along with the best safety for patients.To achieve this goal,therapeutic agents that can differentiate tumors from normal tissues and exert specific and controlled cancer treatments are highly desirable.In this work,we constructed a multifunctional nanoplatform specifically responsive to the acidic tumor microenvironment using polyaniline and indocyanine green(ICG)loaded hollow mesoporous silica nanoparticles.The proton-activable photothermal property facilitates the differentiation and targeted damage of tumor tissues.Then,these nanoparticles generated reactive oxygen species(ROS)and local heat simultaneously upon single laser irradiation to exert a high tumor ablation efficiency.Overall,the combination therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)derived from the multifunctional nanoparticles has realized an elevated therapeutic efficacy compared to one single treatment mode.This unique nanomedicine represents a new design of tumor microenvironment-responsive therapeutical system for efficient cancer treatment,especially for the development of combined nanomedicine for further personalized cancer treatment.展开更多
A series of new nanobiotechnology-based methods have been developed toward achieving safe and efficient cancer treatment.Gold nanorods(AuNRs)have attracted increasing attention owing to their unique optical char-acter...A series of new nanobiotechnology-based methods have been developed toward achieving safe and efficient cancer treatment.Gold nanorods(AuNRs)have attracted increasing attention owing to their unique optical char-acteristics,good biocompatibility,and low toxicity,and they have thus been widely used in tumor treatment.In this study,an AuNR-based system was designed by attaching microRNA-192(miR-192)to polydopamine-coated AuNRs(AuNR@PDA)to explore the possibility of combining genetic and photothermal therapies.RNA/AuNR@PDA exhibited an excellent thermal conversion efficiency under near-infrared(NIR)laser irradi-ation and excellent biocompatibility.Thus,photothermal therapy(PTT)was combined with gene therapy,which was effected by miR-192,a genetic drug that inhibits cancer cell growth.The combinatory treatment approach entailing the AuNRs-based drug carrier system exhibited encouraging antitumor efficacy.展开更多
Bacterial biofilms,especially those caused by multidrug-resistant bacteria,have emerged as one of the greatest dangers to global public health.The acceleration of antimicrobial resistance to conventional an-tibiotics ...Bacterial biofilms,especially those caused by multidrug-resistant bacteria,have emerged as one of the greatest dangers to global public health.The acceleration of antimicrobial resistance to conventional an-tibiotics and the severe lack of new drugs necessitates the development of novel agents for biofilm eradication.Photodynamic therapy(PDT)is a promising non-antibiotic method for treating bacterial infections.However,its application in biofilm eradication is hampered by the hypoxic microenvironment of biofilms and the physical protection of extracellular polymeric substances.In this study,we develop a composite nanoplatform with oxygen(O_(2))self-supplying and heat-sensitizing capabilities to improve the PDT efficacy against biofilms.CaO_(2)/ICG@PDA nanoparticles(CIP NPs)are fabricated by combining calcium peroxide(CaO_(2))with the photosensitizer indocyanine green(ICG)via electrostatic interactions,followed by coating with polydopamine(PDA).The CIP NPs can gradually generate O_(2)in response to the acidic microenvironment of the biofilm,thereby alleviating its hypoxic state.Under near-infrared(NIR)irradiation,the nanoplatform converts O_(2)into a significant amount of singlet oxygen(^(1)O_(2))and heat to eradicate biofilm.The generated heat enhances the release of O_(2),accelerates the generation of^(1)O_(2)in PDT,increases cell membrane permeability,and increases bacterial sensitivity to^(1)O_(2).This nanoplatform significantly improves the efficacy of PDT in eradicating biofilm-dwelling bacteria without fostering drug resistance.Experiments on biofilm eradication demonstrate that this nanoplatform can eradicate over 99.9999%of methicillin-resistant Staphylococcus aureus(MRSA)biofilms under 5-min NIR irradiation.Notably,these integrated advantages enable the system to promote the healing of MRSA biofilm-infected wounds with negligible toxicity in vivo,indicating great promise for overcoming the obstacles associated with bacterial biofilm eradication.展开更多
UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of...UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS_(2) can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS_(2). The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upcon-version emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS_(2) shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/ Nd@NaYF4:Nd@AgBiS_(2) core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/ PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nano-structures for applications such as fighting against cancers.展开更多
Under laser irradiation,photothermal therapy(PTT)effectively ablates tumors above 50℃.However,hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue.Herein,nanopartic...Under laser irradiation,photothermal therapy(PTT)effectively ablates tumors above 50℃.However,hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue.Herein,nanoparticles named as GI@P NPs were designed for enhanced PTT with heat shock protein 90(HSP90)inhibition at temperatures below 50℃to achieve optimal cancer therapy and avoid surrounding damage.GI@P NPs were done by co-loading Garcinia cambogia acid(GA)and photosensitizer IR783 in polymer PLG-g-mPEG to form a nanomedicine,where IR783 with excellent photoacoustic(PA)signal acted as an excellent photothermal therapeutic agent that converted the laser energy into heat to kill tumor cells,GA was used as antitumor drug for chemotherapy and an inhibitor of HSP90 to overcome the heat resistance of tumors for efficient cryo-photothermal therapy,and PLG-g-mPEG can encapsulate IR783 and GA to increase biocompatibility and accumulate effectively in the tumor.After GI@P NPs were injected into the mice,we could observe that the PA signals gradually increased in the tumor region and showed the strongest PA signals at 12 h.Under laser irradiation,the tumor temperature of the mice could raise to about 43.5℃,and the tumor was significantly inhibited after long-term monitoring by PA imaging.As a result,gentle PTT produced by GI@P NPs exhibited good antitumor effects at relatively low temperature and minimized nonspecific thermal damage to normal tissues.The GI@P NPs as nanomedicine enriched our understanding of various applications of polymeric carriers,especially in the biomedical field.展开更多
Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness.Herein,a targeting multifunctional black phosphorus(BP)nanoparticle,modified by PEGylated hyaluronic acid(HA),was ...Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness.Herein,a targeting multifunctional black phosphorus(BP)nanoparticle,modified by PEGylated hyaluronic acid(HA),was designed for photothermal/photodynamic/photo-immunotherapy.In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility,stability,and sufficient therapeutic efficacy in the combined therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)for cancer therapy.Moreover,the results of in vitro showed that HA-BP down-regulated the expression of CD206(M2 macrophage marker)by 42.3%and up-regulated the ratio of CD86(M1 macrophage marker)by 59.6%,indicating that HABP nanoparticles have functions in remodeling tumor associated macrophages(TAMs)phenotype(from protumor M2 TAMs to anti-tumor M1 macrophages).Fluorescence(FL)and photoacoustic(PA)multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44^+mediated active targeting and passive EPR effect.In vitro and in vivo studies suggested that the combined therapy of PDT,PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death(ICD)and release Damage-associated molecular patterns(DAMPs),which could induce maturation of dendritic cells(DCs)and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment.This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.展开更多
Diketopyrrolopyrrole(DPP)derivatived photosensitizers(PSs)with near infrared(NIR)absorption and good photophysical properties have drawn tremendous attention in cancer phototherapy.However,current DPP derivatives pres...Diketopyrrolopyrrole(DPP)derivatived photosensitizers(PSs)with near infrared(NIR)absorption and good photophysical properties have drawn tremendous attention in cancer phototherapy.However,current DPP derivatives present unsatisfactory quantum yield of singlet oxygen(1O2)due to the large energy gap between the excited singlet and triplet states.To tackle this challenge,herein the DPP core is functionalized with triphenylphosphine-Au(I)group(Th DPP-Au),leading to a high1O2 quantum yield of 0.65.Theoretical calculation attributes the enhancement to spin-orbit coupling and population of the triplet excition upon photoexcitation.The hydrophilic Th DPP-Au nanoparticals(NPs)are prepared via nano-reprecipitation,which displays homogeneous size and excellent light absorption ability(ε=4.382×104 M-1cm-1).And the Th DPP-Au NPs exhibit low dark toxicity and high phototoxicity,which can effectively kill tumor cells via 1O2 induced mitochondrial apoptotic pathway upon irradiation.Furthermore,in vivo experiments demonstrate that Th DPP-Au NPs can selective accumulation in tumor and present excellent synergistic photodynamic/photothermal therapy guided by fluorescence and photothermal dual imaging.展开更多
文摘The study developed a mild method to prepare partially reduced graphene oxide(pRGO).Through the non-covalent interaction of pRGO with nucleic acid aptamers AS1411 and indocytinine green(ICG),photothermal and photosensitive nanocomposites pRGO-AS1411-ICG(pRAI)were constructed.The complex structure and morphological characteristics of pRGO and pRAI were used by fourier transform infrared spectroscopy(FTIR),raman spectroscopy(Raman),X-ray photoelectron spectroscopy(XPS),ultraviolet-visible spectroscopy(Uv-vis),and transmission electron microscope(TEM).And the effect of EDS phototherapeutic back heat therapy on tumor cells was carried out in cell experiments.The results showed that pRAI with targeting of AS1411 can effectively kill tumor cells through the dual effects of photothermal therapy(PTT)and photodynamic therapy(PDT).
基金supported from 973 Project (Grant No. 2015CB931802 and 2017YFA0205301)Chinese National Natural Scientific Fund (Grant No.81327002 and 81803094)+1 种基金China Postdoctoral Science Foundation (Grant No. 2017M621486)Funding from Shanghai Engineering Research Center for Intelligent diagnosis and treatment instrument (Grant No.15DZ2252000)
文摘Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.
基金financial support from Fundamental Research Funds for Central Universities (XDJK2016A010 and XDJK2017C001)National Natural Science Foundation of China (51703186 and 31671037)Southwest University (SWU116032 and SWU115059)
文摘Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.
基金Supported by the National Natural Science Foundation of China(No.81373826,No.81100658)Development Project of Science and Technology of Traditional Chinese Medicine of Shandong Province(No.2013ZDZK-083)Development Project of Medicine and Health Science Technology of Shandong Province(No.2013WS0251)
文摘AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTSThree RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study.CONCLUSIONIVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.
基金supported by the National Natural Science Foundation of China (81690264)the National Basic Research Program of China (2015CB932100)the Innovation Team of the Ministry of Education (BMU20110263)。
文摘Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.
文摘AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.
文摘Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performance of photothermalconversion limits the therapeutic effect of combination therapy. In this study, two-dimensional boron (boron, B) nanoparticles wereprepared by ultrasonic exfoliation, and copper sulfide (CuS) nanoparticles and doxorubicin (DOX) were grown on the surface ofthe nanoparticles to form B-CuS-DOX nanoparticles. B-CuS carrier has high DOX drug loading capacity (864mg/g) and goodphotothermal conversion performance (photothermal conversion efficiency at 808nm is 55.8%). At the same time, it can achievedrug release and good photothermal response at near infrared and pH. The nanoparticles designed in this study are expected toprovide an effective chemotherapy-photothermal therapy strategy for tumor therapy in vivo.
基金supported by NSF of Jiangsu Province(No.BK20200092)。
文摘Introducing heavy halogen atoms into organic small molecules is a practical strategy for efficient singlet oxygen(^(1)O_(2))generation.Generally,bromine or iodine atoms are introduced on the aza-borondipyrromethene(aza-BODIPY)core,rather than on the periphery aryl rings for efficient~1O_(2) generation.Herein,an aza-BODIPY dye NBDPBr with unexpected bromination on the periphery aryl rings was synthesized for photoacoustic(PA)imaging-guided synergistic photothermal therapy(PTT)and photodynamic therapy(PDT)in tumor cells.Owing to unexcepted bromination at the periphery aryl rings,NBDPBr demonstrated an outstanding singlet oxygen quantum yield(Φ_(Δ))of 66% which was superior to similar brominated photosensitizers previously reported.After encapsulation with amphiphilic polymer F-127,hydrophilic NBDPBr nanoparticles(NPs)were fabricated and exhibited an excellent photothermal conversion efficiency(η)of 43.0% under 660 nm photoirradiation.In vivo PA imaging results demonstrated that NBDPBr NPs could specifically accumulate at tumor sites and realized the maximum tumor retention at 7 h post-injection.All the in vitro and in vivo results indicated the significant potence of NBDPBr with unexpected bis-bromination for PA imaging-guided synergetic PDT/PTT.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52103196 and 52073060)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038).
文摘Multimodal treatment modalities hold great potential for cancer therapy,thus current efforts are focusing on the development of more effective and practical synergistic therapeutic platforms.Herein,we present a novel trans,trans,trans-[Pt(N_(3))_(2)(OH)_(2)(py)_(2)](Pt(Ⅳ))prodrug-initiated hydrogel microparticles(M_(ICG-Pt))with indocyanine green(ICG)encapsulation by microfluidics for efficiently synergistic chemo-,photothermal(PTT)and photodynamic therapy(PDT).The employed Pt(Ⅳ)could not only serves as an initiator to generate azidyl radical(N_(3)^(·))for photo-polymerization of methacrylate gelatin(GelMA)matrix,but also be reduced to high cytotoxic platinum(Ⅱ)(Pt(Ⅱ))species for tumor chemotherapy.The laden ICG with highly photothermal heating ability and intrinsic reactive oxygen species(ROS)productivity endows the M_(ICG-Pt) with effective PTT/PDT performances upon near-infrared(NIR)light irradiation.In addition,benefiting from the production of oxygen during the photo-activation process of Pt(Ⅳ),the PDT efficacy of ICG-laden M_(ICG-Pt) could be further enhanced.Based on these advantages,we have demonstrated that the M_(ICG-Pt) could significantly eliminate cancer cells in vitro,and remarkably suppressed the tumor growth in vivo via synergistic chemotherapy,PTT,and PDT.These results indicate that such Pt(Ⅳ)-initiated hydrogel microparticles are ideal candidates of multimodal treatment platforms,holding great prospects for cancer therapy.
基金Supported by funds provided by CONICET(PIP 112-201101-00453),SECyT,FONCyT(PICT 2011-1328),and MinCyT Córdoba(PID 2010)
文摘Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to targettumors. Selective therapies can be established by focusing on distinctive intracellular(receptors, apoptotic pathways, multidrug resistance system, nitric oxidemediated stress) and environmental(glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity.
基金Supported by the National Basic Research Program of China(2015CB932100)
文摘Aurum nanomaterials(ANM), combining the features of nanotechnology and metal elements, have demonstrated enormous potential and aroused great attention on biomedical applications over the past few decades. Particularly, their advantages, such as controllable particle size, flexible surface modification, higher drug loading, good stability and biocompatibility, especially unique optical properties, promote the development of ANM in biomedical field. In this review, we will discuss the advanced preparation process of ANM and summarize their recent applications as well as their prospects in diagnosis and therapy. Besides, multi-functional ANM-based theranostic nanosystems will be introduced in details, including radiotherapy(RT), photothermal therapy(PTT), photodynamic therapy(PDT), immunotherapy(IT), and so on.
基金financially supported by Beijing Natural Science Foundation,Haidian,original innovation joint fund(No.17L20170)National Key Research and Development Program of China(No.2016YFA0201400)+3 种基金State Key Program of National Natural Science of China(No.81930047)Projects of International Cooperation and Exchanges NSFC-PSF(No.31961143003)National Project for Research and Development of Major Scientific Instruments(No.81727803)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421004).
文摘Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic.Yet,it suffers from certain limitations during clinical exploitation,including insufficient photosensitizers(PSs)delivery,tumor-oxygenation dependency,and treatment escape of aggressive tumors.To overcome these obstacles,an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles(NPs)by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers.Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation.A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment.This review provides an overview of available data regarding the design,methodology,and oncological outcome of the innovative NPs-based PDT of PCa.
基金support received from Sichuan Science and Technology Program(2019JDJQ0028)。
文摘Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other conditions.PDT not only provide a precise and selective method for the treatment of various diseases by itself,it can also be used in combination with other traditional therapies.Because PDT uses light as the unique targeting mechanism,it has simpler and more direct targeting capability than traditional therapies.The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances.Different photosensitizers have their distinct characteristics,leading to different advantages and disadvantages.These could be enhanced or compensated by using proper PDT system.Therefore,the selected type of photosensitizer would heavily influence the overall design of a PDT system.In this article,we evaluated major types of inorganic and organic PDT photosensitizers,and discussed future research directions in the field.
基金supported by the Natural Science Foundation of Hebei Province(B2021201005,B2022201029)the Medical Science Research Plan Project of Health Commission of Hebei Province(20210623,20211152)the Medical Science Foundation of Hebei University(2020B16,2021X04)
文摘Therapeutic failures are always accompanied by surgery,chemotherapy,and radiotherapy when metastasis or therapeutic resistance is present in tumors.Thus,it is of critical importance to optimize the therapeutic strategy to realize a high curative effect along with the best safety for patients.To achieve this goal,therapeutic agents that can differentiate tumors from normal tissues and exert specific and controlled cancer treatments are highly desirable.In this work,we constructed a multifunctional nanoplatform specifically responsive to the acidic tumor microenvironment using polyaniline and indocyanine green(ICG)loaded hollow mesoporous silica nanoparticles.The proton-activable photothermal property facilitates the differentiation and targeted damage of tumor tissues.Then,these nanoparticles generated reactive oxygen species(ROS)and local heat simultaneously upon single laser irradiation to exert a high tumor ablation efficiency.Overall,the combination therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)derived from the multifunctional nanoparticles has realized an elevated therapeutic efficacy compared to one single treatment mode.This unique nanomedicine represents a new design of tumor microenvironment-responsive therapeutical system for efficient cancer treatment,especially for the development of combined nanomedicine for further personalized cancer treatment.
基金the National Natural Science Foundation of China(Grant Nos.52101287 and U1806219)the Shenzhen Fundamental Research Program(JCYJ20190807092803583)the Natural Science Foundation of Jiangsu Province(Grant No.BK20190205).
文摘A series of new nanobiotechnology-based methods have been developed toward achieving safe and efficient cancer treatment.Gold nanorods(AuNRs)have attracted increasing attention owing to their unique optical char-acteristics,good biocompatibility,and low toxicity,and they have thus been widely used in tumor treatment.In this study,an AuNR-based system was designed by attaching microRNA-192(miR-192)to polydopamine-coated AuNRs(AuNR@PDA)to explore the possibility of combining genetic and photothermal therapies.RNA/AuNR@PDA exhibited an excellent thermal conversion efficiency under near-infrared(NIR)laser irradi-ation and excellent biocompatibility.Thus,photothermal therapy(PTT)was combined with gene therapy,which was effected by miR-192,a genetic drug that inhibits cancer cell growth.The combinatory treatment approach entailing the AuNRs-based drug carrier system exhibited encouraging antitumor efficacy.
基金supported by the National Natural Science Foundation of China(No.22175125)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.21KJA150008)the Key Laboratory of Polymeric Materials De-sign and Synthesis for Biomedical Function,Soochow University,and the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Bacterial biofilms,especially those caused by multidrug-resistant bacteria,have emerged as one of the greatest dangers to global public health.The acceleration of antimicrobial resistance to conventional an-tibiotics and the severe lack of new drugs necessitates the development of novel agents for biofilm eradication.Photodynamic therapy(PDT)is a promising non-antibiotic method for treating bacterial infections.However,its application in biofilm eradication is hampered by the hypoxic microenvironment of biofilms and the physical protection of extracellular polymeric substances.In this study,we develop a composite nanoplatform with oxygen(O_(2))self-supplying and heat-sensitizing capabilities to improve the PDT efficacy against biofilms.CaO_(2)/ICG@PDA nanoparticles(CIP NPs)are fabricated by combining calcium peroxide(CaO_(2))with the photosensitizer indocyanine green(ICG)via electrostatic interactions,followed by coating with polydopamine(PDA).The CIP NPs can gradually generate O_(2)in response to the acidic microenvironment of the biofilm,thereby alleviating its hypoxic state.Under near-infrared(NIR)irradiation,the nanoplatform converts O_(2)into a significant amount of singlet oxygen(^(1)O_(2))and heat to eradicate biofilm.The generated heat enhances the release of O_(2),accelerates the generation of^(1)O_(2)in PDT,increases cell membrane permeability,and increases bacterial sensitivity to^(1)O_(2).This nanoplatform significantly improves the efficacy of PDT in eradicating biofilm-dwelling bacteria without fostering drug resistance.Experiments on biofilm eradication demonstrate that this nanoplatform can eradicate over 99.9999%of methicillin-resistant Staphylococcus aureus(MRSA)biofilms under 5-min NIR irradiation.Notably,these integrated advantages enable the system to promote the healing of MRSA biofilm-infected wounds with negligible toxicity in vivo,indicating great promise for overcoming the obstacles associated with bacterial biofilm eradication.
基金This work was financially supported by the National Natural Science Foundation of China(Grants 52172276,U20A20379),research fund from Anhui Provincial Institute of Translational Medicine(2021zhyx-B15)Grants for Scientific Research of BSKY(No:XJ201933)from Anhui Medical University.Zhaoyou Chu,Tian Tian,and Zhenchao Tao contributed equally to this work.
文摘UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS_(2) can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS_(2). The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upcon-version emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS_(2) shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/ Nd@NaYF4:Nd@AgBiS_(2) core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/ PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nano-structures for applications such as fighting against cancers.
基金the National Natural Science Foundation of China(Nos.52173115,52073278,51925305 and 51873208)Jilin province science and technology development program(No.20200201103JC)Foundation of Department of Education of Jilin Province of China(No.JJKH20210828KJ).
文摘Under laser irradiation,photothermal therapy(PTT)effectively ablates tumors above 50℃.However,hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue.Herein,nanoparticles named as GI@P NPs were designed for enhanced PTT with heat shock protein 90(HSP90)inhibition at temperatures below 50℃to achieve optimal cancer therapy and avoid surrounding damage.GI@P NPs were done by co-loading Garcinia cambogia acid(GA)and photosensitizer IR783 in polymer PLG-g-mPEG to form a nanomedicine,where IR783 with excellent photoacoustic(PA)signal acted as an excellent photothermal therapeutic agent that converted the laser energy into heat to kill tumor cells,GA was used as antitumor drug for chemotherapy and an inhibitor of HSP90 to overcome the heat resistance of tumors for efficient cryo-photothermal therapy,and PLG-g-mPEG can encapsulate IR783 and GA to increase biocompatibility and accumulate effectively in the tumor.After GI@P NPs were injected into the mice,we could observe that the PA signals gradually increased in the tumor region and showed the strongest PA signals at 12 h.Under laser irradiation,the tumor temperature of the mice could raise to about 43.5℃,and the tumor was significantly inhibited after long-term monitoring by PA imaging.As a result,gentle PTT produced by GI@P NPs exhibited good antitumor effects at relatively low temperature and minimized nonspecific thermal damage to normal tissues.The GI@P NPs as nanomedicine enriched our understanding of various applications of polymeric carriers,especially in the biomedical field.
基金This work was supported by the National Natural Science Foundation of China(51773231)the Natural Science Foundation of Guangdong Province(2014A030312018,2016A030313315)the Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province(2011A060901013).
文摘Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness.Herein,a targeting multifunctional black phosphorus(BP)nanoparticle,modified by PEGylated hyaluronic acid(HA),was designed for photothermal/photodynamic/photo-immunotherapy.In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility,stability,and sufficient therapeutic efficacy in the combined therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)for cancer therapy.Moreover,the results of in vitro showed that HA-BP down-regulated the expression of CD206(M2 macrophage marker)by 42.3%and up-regulated the ratio of CD86(M1 macrophage marker)by 59.6%,indicating that HABP nanoparticles have functions in remodeling tumor associated macrophages(TAMs)phenotype(from protumor M2 TAMs to anti-tumor M1 macrophages).Fluorescence(FL)and photoacoustic(PA)multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44^+mediated active targeting and passive EPR effect.In vitro and in vivo studies suggested that the combined therapy of PDT,PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death(ICD)and release Damage-associated molecular patterns(DAMPs),which could induce maturation of dendritic cells(DCs)and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment.This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.
基金supported by the National Natural Science of Foundation of China(61525402,61775095,21704043)Jiangsu Provincial Key Research and Development Plan(BE2017741)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20170990,17KJB150020)the Six talent peak innovation team in Jiangsu Province(TD-SWYY-009)
文摘Diketopyrrolopyrrole(DPP)derivatived photosensitizers(PSs)with near infrared(NIR)absorption and good photophysical properties have drawn tremendous attention in cancer phototherapy.However,current DPP derivatives present unsatisfactory quantum yield of singlet oxygen(1O2)due to the large energy gap between the excited singlet and triplet states.To tackle this challenge,herein the DPP core is functionalized with triphenylphosphine-Au(I)group(Th DPP-Au),leading to a high1O2 quantum yield of 0.65.Theoretical calculation attributes the enhancement to spin-orbit coupling and population of the triplet excition upon photoexcitation.The hydrophilic Th DPP-Au nanoparticals(NPs)are prepared via nano-reprecipitation,which displays homogeneous size and excellent light absorption ability(ε=4.382×104 M-1cm-1).And the Th DPP-Au NPs exhibit low dark toxicity and high phototoxicity,which can effectively kill tumor cells via 1O2 induced mitochondrial apoptotic pathway upon irradiation.Furthermore,in vivo experiments demonstrate that Th DPP-Au NPs can selective accumulation in tumor and present excellent synergistic photodynamic/photothermal therapy guided by fluorescence and photothermal dual imaging.