The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HE...The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HER-2)overexpressing breast cancer treatment.However,insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical application.Herein,an in situ forming gold nanorods(AuNRs)-sodium alginate(ALG)hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable,dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic therapy.The photothermal agent AuNRs,anticancer drug DOX,and anticancer antibody HCT were mixed in ALG solution,and after injection,the soluble ALG was quickly transformed into a hydrogel in the presence of Ca^(2+)in the body.Significantly,the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70%under 808 nm laser irradiation.The thermal effect can also provide photothermal stimulation to trigger the drug release from the gel matrix.In addition,the drug release rate and the releasing degree are also sensitive to the pH.In vitro studies demonstrated that the PEI-AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK-BR-3 cells.In vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor sites.The proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER-2 overexpressing cancer therapy.展开更多
The abundant intracellular glutathione(GSH)in cancer cells severely undermines the therapeutic efficacy of different treatments due to their role in protecting cancer cells from the associated oxidative stress.Develop...The abundant intracellular glutathione(GSH)in cancer cells severely undermines the therapeutic efficacy of different treatments due to their role in protecting cancer cells from the associated oxidative stress.Developing a highly integrated system to consume GSH would help to improve the therapeutic outcomes.In this study,supramolecular prodrug self-assemblies(SPSAs)with IR825 loaded inside were developed to consume GSH via two-pronged pathways while augmenting the therapeutic potency of chemo/photothermal treatment.SPSAs were prepared using water-soluble pillar[6]arene(WP[6])as host units and H_(2)O_(2)-responsive nitrogen mustard prodrug,chlorambucil-(phenylboronic acid pinacol ester)conjugates(Cb-BE),as the guests.When SPSAs were internalized by cancer cells,the generation of quinone methide(QM)from Cb-BE and singlet oxygen(^(1)O_(2))from irradiation-activated IR825 could consume GSH in a concerted way.As such,the therapeutic efficacies of the released chlorambucil and the accompanied hyperthermia were augmented toward synergistically inhibiting tumor growth.展开更多
Nanozymes are nanomaterials with enzyme-like properties that have attracted significant interest owing to their high stability,easy preparation,and tunable catalytic properties,especially in the field of cancer therap...Nanozymes are nanomaterials with enzyme-like properties that have attracted significant interest owing to their high stability,easy preparation,and tunable catalytic properties,especially in the field of cancer therapy.However,the unfavorable catalytic effects of nanozymes in the acidic tumor microenvironment have limited their applications.Herein,we developed a biomimetic erythrocyte membrane-camouflaged ultrasmall black phosphorus quantum dots(BPQDs)nanozymes that simultaneously exhibited an exceptional near-infrared(NIR)photothermal property and dramatically photothermal-enhanced glucose oxidase(GOx)-like activity in the acidic tumor microenvironment.We demonstrated the engineered BPQDs gave a photothermal conversion efficiency of 28.9%that could rapidly heat the tumor up to 50℃ while effectively localized into tumors via homing peptide iRGD leading after intravenously injection.Meanwhile,the significantly enhanced GOx-like activity of BPQDs under NIR irradiation was capable of catalytical generating massive toxic reactive oxygen species via using cellular glucose.By combining the intrinsic photothermal property and the unique photothermal-enhanced GOx-like catalytic activity,the developed BPQDs were demonstrated to be an effective therapeutic strategy for inhibiting tumor growth in vivo.We believe that this work will provide a novel perspective for the development of nanozymes in tumor catalytic therapy.展开更多
Gallium-based liquid metals have attracted significant interest in the biomedical field due to their unique properties such as low viscosity,good fluidity,high thermal/electrical conductivity,and good biocompatibility...Gallium-based liquid metals have attracted significant interest in the biomedical field due to their unique properties such as low viscosity,good fluidity,high thermal/electrical conductivity,and good biocompatibility.Meanwhile,photothermal therapy has made great development in the field of antitumor with its advantages of low adverse effects,high specificity,and repeatable treatment.The photothermal capability possessed by gallium-based liquid metals makes them show unparalleled advantages in photothermal therapy.Liquid metal-based photothermal therapy has progressed in recent years and can perform a vital role in accurate and noninvasive antitumor therapy.Herein,a review of the major preparation methods of liquid metal micro/nanoparticles,the mechanism of liquid metal photothermal conversion,and discussions on the factors affecting the photothermal properties of liquid metals are presented.The biological applications of liquid metal photothermal therapy in synergy with other therapies are discussed,as well as the current challenges and opportunities for the clinical translation of liquid metals in biomedical applications.展开更多
Applying the fluorescent carbon dots as smart materials in anticancer therapy is of great interest.However,carbon dots for multimodal synergistic anticancer therapy,especially for the triple modality,is rarely reporte...Applying the fluorescent carbon dots as smart materials in anticancer therapy is of great interest.However,carbon dots for multimodal synergistic anticancer therapy,especially for the triple modality,is rarely reported.Herein,we successfully synthesized OCDs by citric acid and(1R,2S)-2-amino-1,2-diphenylethan-1-ol,which show aggregation-induced emission property and two-photon fluorescence imaging.Meanwhile,OCDs are ideal photosensitizers for photothermal therapy under 808 nm and TypeⅠphotodynamic therapy with white light.Hydroxyl radicals,generated by TypeⅠphotodynamic therapy based on OCDs can transform protumoral M2 macrophages into antitumoral M1 macrophages,which exhibited immunotherapy ability.The synergism trimodal of OCDs results in potent anticancer efficacy,showing great potential in cancer therapy.展开更多
Building self-assembly nanostructures is an important way to overcome the limitations of paclitaxel in tumor therapy.However,this strategy is also faced with challenges,such as difficulties in efficient release and th...Building self-assembly nanostructures is an important way to overcome the limitations of paclitaxel in tumor therapy.However,this strategy is also faced with challenges,such as difficulties in efficient release and the potential for drug resistance.Herein,we developed a near-infrared light-activatable melanized paclitaxel self-assembly nanoparticles for synergistic anti-tumor therapy.In this strategy,paclitaxel dimer prodrugs were synthesized and paclitaxel nanoparticles were obtained through self-assembly.Finally,the paclitaxel dimer nanoparticles were capped with polydopamine(PDA,melanoidin)and human serum albumin(HSA).The disulfide bonds in paclitaxel dimeric prodrug specifically respond to high concentrations of glutathione(GSH)and reactive oxygen species(ROS)in tumor cells.PDA enhances the biocompatibility of the drug molecules and imparts near-infrared photothermal conversion capability to the nano-self-assemblies.Both the in vitro and in vivo experiments demonstrated that this paclitaxel nanoprodrug exhibited enhanced tumor therapeutic efficacy under near-infrared light irradiation.展开更多
Multimodal combinatorial therapy merges different modes of therapies in one platform,which can overcome several clinical challenges such as premature drug loss during blood circulation and significantly improve treatm...Multimodal combinatorial therapy merges different modes of therapies in one platform,which can overcome several clinical challenges such as premature drug loss during blood circulation and significantly improve treatment efficiency.Here we report a combinatorial therapy nanoplatform that enables dual photothermal therapy and pH-stimulus-responsive chemotherapy.By super-assembly of mesoporous silica nanoparticles(MSN)with metal-phenolic networks(MPN),anti-cancer drugs can be loaded in the MSN matrix,while the outer MPN coating allows dual photothermal and pH-responsive properties.Upon near-infrared light irradiation,the MSN@MPN nanoplatform exhibits excellent photothermal effect,and demonstrates outstanding pH-triggered drug release property.In vitro cell experiments suggest the MSN@MPN system exhibits superior biocompatibility and can effectively kill tumor cells after loading anti-cancer drugs.Consequently,the MSN@MPN system shows promising prospects in clinical application for tumor therapy.展开更多
Malignant tumor has become an urgent threat to global public healthcare.Because of the heterogeneity of tumor,single therapy presents great limitations while synergistic therapy is arousing much attention,which shows ...Malignant tumor has become an urgent threat to global public healthcare.Because of the heterogeneity of tumor,single therapy presents great limitations while synergistic therapy is arousing much attention,which shows desperate need of intelligent carrier for co-delivery.A core-shell dual metaleorganic frameworks(MOFs)system was delicately designed in this study,which not only possessed the unique properties of both materials,but also provided two individual specific functional zones for co-drug delivery.Photosensitizer indocyanine green(ICG)and chemotherapeutic agent doxorubicin(DOX)were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform.Except for efficient drug delivery,the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy.The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared(NIR)light irradiation.The in vivo antitumor study showed superior synergistic antitumor effect by concentrating the nanoparticles into dissolving microneedles as compared to intravenous and intratumoral injection of nanoparticles,with a significantly higher inhibition rate.It is anticipated that the multi-model synergistic system based on dual-MOFs was promising for further biomedical application.展开更多
基金support from the National Natural Science Foundation of China (Nos.52101287 and U1806219)the Shenzhen Fundamental Research Program (No.JCYJ20190807092803583)+1 种基金the Natural Science Foundation of Jiangsu Province (No.BK20190205)supported by the Special Funding in the Project of the Taishan Scholar Construction Engineering and the Program of Jinan Science and Technology Bureau (No.2020GXRC019)as well as New Material Demonstration Platform Construction Project from the Ministry of Industry and Information Technology (No.2020-370104-34-03-043952-01-11).
文摘The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HER-2)overexpressing breast cancer treatment.However,insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical application.Herein,an in situ forming gold nanorods(AuNRs)-sodium alginate(ALG)hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable,dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic therapy.The photothermal agent AuNRs,anticancer drug DOX,and anticancer antibody HCT were mixed in ALG solution,and after injection,the soluble ALG was quickly transformed into a hydrogel in the presence of Ca^(2+)in the body.Significantly,the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70%under 808 nm laser irradiation.The thermal effect can also provide photothermal stimulation to trigger the drug release from the gel matrix.In addition,the drug release rate and the releasing degree are also sensitive to the pH.In vitro studies demonstrated that the PEI-AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK-BR-3 cells.In vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor sites.The proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER-2 overexpressing cancer therapy.
基金This work was supported by the National Natural Science Foundation of China(Nos.21801162,22277011,and 22107019)National Key Research&Development Program of China(No.2020YFA0210800)+1 种基金National Science Basic Research Plan in Shaanxi Province of China(No.2023-JC-QN-0150)the Major Project of Science and Technology of Fujian Province(No.2020HZ06006).
文摘The abundant intracellular glutathione(GSH)in cancer cells severely undermines the therapeutic efficacy of different treatments due to their role in protecting cancer cells from the associated oxidative stress.Developing a highly integrated system to consume GSH would help to improve the therapeutic outcomes.In this study,supramolecular prodrug self-assemblies(SPSAs)with IR825 loaded inside were developed to consume GSH via two-pronged pathways while augmenting the therapeutic potency of chemo/photothermal treatment.SPSAs were prepared using water-soluble pillar[6]arene(WP[6])as host units and H_(2)O_(2)-responsive nitrogen mustard prodrug,chlorambucil-(phenylboronic acid pinacol ester)conjugates(Cb-BE),as the guests.When SPSAs were internalized by cancer cells,the generation of quinone methide(QM)from Cb-BE and singlet oxygen(^(1)O_(2))from irradiation-activated IR825 could consume GSH in a concerted way.As such,the therapeutic efficacies of the released chlorambucil and the accompanied hyperthermia were augmented toward synergistically inhibiting tumor growth.
基金Acknowledgements This work has been financially supported by the National Natural Science Foundation of China （Nos. 51372260, 51132009, and 21172043）, the Shanghai Rising-Star Program （No. 12QH1402500）, the Science and Technology Commission of Shanghai （No. 11nm0505000 and 124119a0400）, the Shanghai Municipal Commission of Health （No. 20134360）, the Development Foundation for Talents of Shanghai （No. 2012035）.
基金supported by the National Key Research and Development Program of China(Nos.2020YFC1316900 and 2020YFC1316901)China Postdoctoral Science Foundation(Nos.2019T120754 and 2018M633229)+5 种基金Sanming Project of Medicine in Shenzhen(No.SZSM201612031)National Natural Science Foundation of China(Nos.82003303 and 81722024)National Key R&D Program of China(No.2017YFA0205501)Natural Science Foundation of Guangdong Province of China(Nos.2018A030310665 and 2018A0303130295)Shenzhen Science and Technology Innovation Committee(Nos.JSGG20191129144225464,JCYJ20190806163814395,ZDSYS201707281114196,JCYJ20170306091657539,JCYJ-20170413162242627,JCYJ20170306091452714,and GJHZ-20170313172439851)Development and Reform Commission of Shenzhen Municipality(No.S2016005470013).
文摘Nanozymes are nanomaterials with enzyme-like properties that have attracted significant interest owing to their high stability,easy preparation,and tunable catalytic properties,especially in the field of cancer therapy.However,the unfavorable catalytic effects of nanozymes in the acidic tumor microenvironment have limited their applications.Herein,we developed a biomimetic erythrocyte membrane-camouflaged ultrasmall black phosphorus quantum dots(BPQDs)nanozymes that simultaneously exhibited an exceptional near-infrared(NIR)photothermal property and dramatically photothermal-enhanced glucose oxidase(GOx)-like activity in the acidic tumor microenvironment.We demonstrated the engineered BPQDs gave a photothermal conversion efficiency of 28.9%that could rapidly heat the tumor up to 50℃ while effectively localized into tumors via homing peptide iRGD leading after intravenously injection.Meanwhile,the significantly enhanced GOx-like activity of BPQDs under NIR irradiation was capable of catalytical generating massive toxic reactive oxygen species via using cellular glucose.By combining the intrinsic photothermal property and the unique photothermal-enhanced GOx-like catalytic activity,the developed BPQDs were demonstrated to be an effective therapeutic strategy for inhibiting tumor growth in vivo.We believe that this work will provide a novel perspective for the development of nanozymes in tumor catalytic therapy.
基金the financial support from the National Natural Science Foundation of China(Nos.52072095 and 92163109)the Shenzhen Science and Technology Program(Nos.JCYJ20200109113408066,KQTD20170809110344233,and RCBS20210609103646022)+2 种基金Shenzhen Bay Laboratory(No.SZBL2019062801005)the Fundamental Research Funds for the Central Universities(No.HIT.OCEF.2021032)the GuangDong Basic and Applied Basic Research Foundation(No.2021A1515110272).
文摘Gallium-based liquid metals have attracted significant interest in the biomedical field due to their unique properties such as low viscosity,good fluidity,high thermal/electrical conductivity,and good biocompatibility.Meanwhile,photothermal therapy has made great development in the field of antitumor with its advantages of low adverse effects,high specificity,and repeatable treatment.The photothermal capability possessed by gallium-based liquid metals makes them show unparalleled advantages in photothermal therapy.Liquid metal-based photothermal therapy has progressed in recent years and can perform a vital role in accurate and noninvasive antitumor therapy.Herein,a review of the major preparation methods of liquid metal micro/nanoparticles,the mechanism of liquid metal photothermal conversion,and discussions on the factors affecting the photothermal properties of liquid metals are presented.The biological applications of liquid metal photothermal therapy in synergy with other therapies are discussed,as well as the current challenges and opportunities for the clinical translation of liquid metals in biomedical applications.
基金financially supported by the National Natural Science Foundation of China(Nos.21905021,U21A20308)Sichuan Science and Technology Support Program(Nos.2022NSFSC1269,2023NSF1977,2023NSFSC0637,2022ZYD0048,2021ZDYF3218,2021YFG0291,2021YFH0132)Sichuan Students’Platform for innovation and entrepreneurship training program(No.202210623013)。
文摘Applying the fluorescent carbon dots as smart materials in anticancer therapy is of great interest.However,carbon dots for multimodal synergistic anticancer therapy,especially for the triple modality,is rarely reported.Herein,we successfully synthesized OCDs by citric acid and(1R,2S)-2-amino-1,2-diphenylethan-1-ol,which show aggregation-induced emission property and two-photon fluorescence imaging.Meanwhile,OCDs are ideal photosensitizers for photothermal therapy under 808 nm and TypeⅠphotodynamic therapy with white light.Hydroxyl radicals,generated by TypeⅠphotodynamic therapy based on OCDs can transform protumoral M2 macrophages into antitumoral M1 macrophages,which exhibited immunotherapy ability.The synergism trimodal of OCDs results in potent anticancer efficacy,showing great potential in cancer therapy.
基金financially supported by National Natural Science Foundation of China(NSFC)(22007083)Zhejiang Provincial Innovation Center of Advanced Textile Technology and the Fundamental Research Funds of Shaoxing Keqiao Research Institute of Zhejiang Sci-Tech University(KYY2022004C)the Fundamental Research Funds of Shengzhou Innovation Research Institute of Zhejiang SciTech University(SYY2023B000004)
文摘Building self-assembly nanostructures is an important way to overcome the limitations of paclitaxel in tumor therapy.However,this strategy is also faced with challenges,such as difficulties in efficient release and the potential for drug resistance.Herein,we developed a near-infrared light-activatable melanized paclitaxel self-assembly nanoparticles for synergistic anti-tumor therapy.In this strategy,paclitaxel dimer prodrugs were synthesized and paclitaxel nanoparticles were obtained through self-assembly.Finally,the paclitaxel dimer nanoparticles were capped with polydopamine(PDA,melanoidin)and human serum albumin(HSA).The disulfide bonds in paclitaxel dimeric prodrug specifically respond to high concentrations of glutathione(GSH)and reactive oxygen species(ROS)in tumor cells.PDA enhances the biocompatibility of the drug molecules and imparts near-infrared photothermal conversion capability to the nano-self-assemblies.Both the in vitro and in vivo experiments demonstrated that this paclitaxel nanoprodrug exhibited enhanced tumor therapeutic efficacy under near-infrared light irradiation.
基金This work was supported by the National Key Research and Development Program of China(Nos.2019YFC1604600,2017YFA0206901,2017YFA0206900)the National Natural Science Foundation of China(Nos.21705027,21974029,81830052),the Construction project of Shanghai Key Laboratory of Molecular Imaging(No.18DZ2260400)+3 种基金the Shanghai Municipal Education Commission(Class II Plateau Disciplinary C onstruction Program of Medical Technology of SUMHS,2018-2020)the Australia National Health and Medical Research Council(NHMRC)(No.APP1163786)the Scientia Fellowship program at UNSW,the MCTL Visiting Fellowship Program,Shanghai Key Laboratory of Molecular Imaging(No.18DZ2260400)the Natural Science Foundation of Shanghai,and the Recruitm ent Program of Global Experts of China and Shanghai.
文摘Multimodal combinatorial therapy merges different modes of therapies in one platform,which can overcome several clinical challenges such as premature drug loss during blood circulation and significantly improve treatment efficiency.Here we report a combinatorial therapy nanoplatform that enables dual photothermal therapy and pH-stimulus-responsive chemotherapy.By super-assembly of mesoporous silica nanoparticles(MSN)with metal-phenolic networks(MPN),anti-cancer drugs can be loaded in the MSN matrix,while the outer MPN coating allows dual photothermal and pH-responsive properties.Upon near-infrared light irradiation,the MSN@MPN nanoplatform exhibits excellent photothermal effect,and demonstrates outstanding pH-triggered drug release property.In vitro cell experiments suggest the MSN@MPN system exhibits superior biocompatibility and can effectively kill tumor cells after loading anti-cancer drugs.Consequently,the MSN@MPN system shows promising prospects in clinical application for tumor therapy.
基金This work was supported by the Fundamental Research Funds for the Central Universities(YD2060002015)the National Natural Science Foundation of China(51873201,82172071)the Key Research and Development Program of Anhui Province(202104b11020025).
基金supported by the National Nature Science Foundation of China(Grant Nos.81773660 and 81803466)the Research and Development Plan for Key Areas in Guangdong Province(Grant No.2019B020204002,China)Natural Science Foundation of Guangdong Province(Grant No.2018A030310095,China)
文摘Malignant tumor has become an urgent threat to global public healthcare.Because of the heterogeneity of tumor,single therapy presents great limitations while synergistic therapy is arousing much attention,which shows desperate need of intelligent carrier for co-delivery.A core-shell dual metaleorganic frameworks(MOFs)system was delicately designed in this study,which not only possessed the unique properties of both materials,but also provided two individual specific functional zones for co-drug delivery.Photosensitizer indocyanine green(ICG)and chemotherapeutic agent doxorubicin(DOX)were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform.Except for efficient drug delivery,the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy.The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared(NIR)light irradiation.The in vivo antitumor study showed superior synergistic antitumor effect by concentrating the nanoparticles into dissolving microneedles as compared to intravenous and intratumoral injection of nanoparticles,with a significantly higher inhibition rate.It is anticipated that the multi-model synergistic system based on dual-MOFs was promising for further biomedical application.
