Nanoparticle-mediated synergistic anticancer effect of ferroptosis and photodynamic therapy:Novel insights and perspectives

Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment.Photodynamic therapy(PDT)causes irreversible chemical damage to target lesions and is widely used in antitumor therapy.However,PDT’s effectiveness is usually hindered by several obstacles,such as hypoxia,excess glutathione(GSH),and tumor resistance.Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species(ROS)or reducing GSH levels,and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment(TME).Strategies based on nanoparticles(NPs)can subtly exploit the potential synergy of ferroptosis and PDT.This review explores recent advances and current challenges in the landscape of the underlyingmechanisms regulating ferroptosis and PDT,as well as nano delivery system-mediated synergistic anticancer activity.These include polymers,biomimetic materials,metal organic frameworks(MOFs),inorganics,and carrier-free NPs.Finally,we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.

Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor

Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsive multifunctional nanoplatform(Bi2S3@Bi@PDA-HA/Art NRs)was presented for synergistic photothermal therapy(PTT),chemodynamic therapy(CDT),and photodynamic therapy(PDT)to achieve better therapeutic outcomes.The Z-scheme heterostructured bismuth sulfide@bismuth nanorods(Bi2S3@Bi NRs)guaranteed excellent photothermal performance of the nanoplatform.Moreover,its ability to produce O2 and reactive oxygen species(ROS)synchronously could relieve tumor hypoxia and improve PDT outcomes.The densely coated polydopamine/ammonium bicarbonate(PDA/ABC)and hyaluronic acid(HA)layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ“bomb-like”release of Art.The CDT treatment was achieved by activating the released Art through intracellular Fe2+ions in an H2O2-independent manner.Furthermore,decreasing the glutathione peroxidase 4(GPX4)levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs.Owing to the synergistic effect,this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo.Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.

Bacteria-Mediated Synergistic Cancer Therapy:Small Microbiome Has a Big Hope

The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.

A computer-aided chem-photodynamic drugs self-delivery system for synergistically enhanced cancer therapy

The therapeutic strategy that gives consideration to the combination of photodynamic therapy and chemotherapy,has emerged as a potential development of effective anti-cancer medicine.Nevertheless,co-delivery of photosensitizers(PSs)and chemotherapeutic drugs in traditional carriers still remains great limitations due to low drug loadings and poor biocompatibility.Herein,we have utilized a computer-aided strategy to achieve a desired carrier-free self-delivery of pyropheophorbide a(PPa,a common PS)and podophyllotoxin(PPT,a classical chemotherapeutic drug)for synergistic cancer therapy.First,the computational simulation method identified the similar molecular sizes and rigid molecular structures between two drugs molecules.Based on the molecular docking,the intermolecular interactions were found to includeπ-πstackings,hydrophobic interactions and hydrogen bonds.Next,both drugs could co-assemble into nanoparticles(NPs)via one-step nanoprecipitation method.The various spectral experiments(UV,IR and FL)were conducted to evaluate the formation mechanism of spherical NPs.Moreover,in vitro and in vivo experiments systematically demonstrated that PPT/PPa NPs not only showed better cellular uptake efficiency,stronger cytotoxicity and higher accumulation in tumor sites,but also exhibited synergistic antitumor effect in female BALB/C bearing-4T1 tumor mice.Such a computer-aided design strategy of chem-photodynamic drugs self-delivery systems pave the way for efficient synergistic cancer therapy.

A proton-catalyzing prodrug for PDT and glycolysis inhibition-synergistic therapy of tumor in spatiotemporal dimensions

The reactive oxygen species(ROS)generation from photosensitizer in photodynamic therapy(PDT)is limited by tumor hypoxia.Even type-I photosensitizers,e.g.,sulfur-substituted Nile blue,still rely on oxygen as the main center for transferring electrons to generate ROS.Cutting off the pathway of oxygen consumption in tumor can help photosensitizers overcome the limitation of low oxygen,in order to efficiently generate more ROS.It is known that glycolysis inhibitor 3-bromopyruvic acid(3-BP),which could specially target mitochondria,can provide more oxygen by inhibiting oxidative phosphorylation.Herein,we successfully designed and synthesized a new 3-BP-coupled sulfur-substituted Nile blue as prodrug(NBBP)for chemical/photodynamic synergistic therapy.Major results indicated that the protons in tumor catalyzed the hydrolysis of NBBP,inhibited photoinduced electron transfer between 3-BP and the photosensitizer in NBBP and further assisted the photosensitizer to be localized in mitochondria,utilizing local oxygen as much as possible and kill tumor cells more efficiently.Moreover,the glycolysis inhibition-induced autophagy was combined with PDT-induced autophagy,which could promote the deaths of tumor cells.Unlike other remedies exploiting nanomaterials,this construction method of NBBP achieves the efficient synergy of photodynamic therapy and glycolysis inhibition,stronger than their theoretical addition,in spatiotemporal dimensions.Our study provides not only a highly efficient platform for tumor therapy but also a design approach for prodrugs with synergistic effects.

Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma

Osteosarcoma(OS)is one of the most common malignant tumors in children and young adults.As chemotherapy and other therapies are limited by low therapeutic efficiency,severe side effects and single therapeutic function,it is of high value to develop innovative therapies for precise and efficient treatment of OS.Herein,natural photo-synthetic microalgae(C.vulgaris,CV)were utilized as carriers for the chemotherapeutic agent doxorubicin(DOX)to create a multifunctional therapeutic platform(CV@DOX)for the photo-modulation of the tumor microenvi-ronment(TME)and synergistic chemo-photodynamic therapy of osteosarcoma.CV@DOX exhibited rapid drug release behavior in the acidic TME,improving the efficiency of chemotherapy against tumors and reducing side effects on other normal tissues.Under 650 nm laser irradiation,CV@DOX demonstrated the ability to effectively generate oxygen to alleviate tumor hypoxia and utilize the photosensitizing properties of chlorophyll in CV to produce an increased amount of reactive oxygen species(ROS),thereby enhancing photodynamic therapy(PDT).CV@DOX-mediated synergistic chemo-photodynamic therapy demonstrated efficacy in halting tumor progression in an orthotopic osteosarcoma mouse model by promoting tumor cell apoptosis,inhibiting tumor proliferation and angiogenesis.Moreover,chlorophyll-assisted fluorescence imaging enabled monitoring of the distribution of CV@DOX in osteosarcoma after administration.Finally,CV@DOX did not cause significant hematological and tissue toxicity,and prevented DOX-induced cardiotoxicity,showing good in vivo biocompatibility.Overall,this work presents a novel TME-responsive and TME-modulating platform for imaging-guided multimodal osteosar-coma treatment.

CRISPR-Cas9 gene editing strengthens cuproptosis/chemodynamic/ferroptosis synergistic cancer therapy

Copper-based nanomaterials demonstrate promising potential in cancer therapy.Cut efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione,initiating chemical dynamic therapy(CDT)and ferroptosis.Cuproptosis,a newly identified cell death modality that represents a great prospect in cancer therapy,is activated.However,active homeostatic systems rigorously keep copper levels within cells exceptionally low,which hinders the application of cooper nanomaterials-based therapy.Herein,a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is developed.The Cu2O and organosilica shell would degrade under the high level of glutathione and weak acidic environment,further releasing RNP and Cut.The liberated Cut triggered a Fenton-like reaction for CDT and partially transformed to Cu2t,consuming intracellular GSH and initiating cuproptosis and ferroptosis efficiently.Meanwhile,the release of RNP effectively reduced the expression of copper transporter ATP7A,subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT,cuproptosis,and ferroptosis.Such tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis.

Play therapy in children with autism:Its role,implications,and limitations

Play is a pleasurable physical or mental activity that enhances the child’s skills involving negotiation abilities,problem-solving,manual dexterity,sharing,decision-making,and working in a group.Play affects all the brain's areas,structures,and functions.Children with autism have adaptive behavior,adaptive response,and social interaction limitations.This review explores the different applications of play therapy in helping children with autism disorder.Play is usually significantly impaired in children with autism.Play therapy is mainly intended to help children to honor their unique mental abilities and developmental levels.The main aim of play therapy is to prevent or solve psychosocial difficulties and achieve optimal child-healthy growth and development.Play therapy helps children with autism to engage in play activities of their interest and choice to express themselves in the most comfortable ways.It changes their way of self-expression from unwanted behaviors to more non-injurious expressive behavior using toys or activities of their choice as their words.Play therapy also helps those children to experience feeling out various interaction styles.Every child with autism is unique and responds differently.Therefore,different types of intervention,like play therapy,could fit the differences in children with autism.Proper evaluation of the child is mandatory to evaluate which type fits the child more than the others.This narrative review revised the different types of play therapy that could fit children with autism in an evidence-based way.Despite weak evidence,play therapy still has potential benefits for patients and their families.

Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma

AIM: To determine whether IFN-α is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN-α for its synergistic properties.METHODS: Eight pancreatic carcinoma cell lines were treated with the single agents and combinations of these.The role of IFN-α regarding a) direct inhibitory effects; b)radio and chemosensitizing effects; c) anti-angiogenic properties and d) enhancement of immunogenicity was investigated.RESULTS: Our results show that IFN-α has direct inhibitory properties and some synergistic influence as determined by AnnexinV/PI stain and cell count. IFN-α is also able to prevent the increase in proliferation rate and VEGF secretion of CDDP resistant cells. Having taken the results from immunogenicity experiments together, we found cells that can be influenced by IFN-α but were less susceptible against T cells. Furthermore, high expression of MHC molecules, CD118, EGF-R and Fas was predictive for a good response.CONCLUSION: In conclusion, IFN-α has direct cytotoxic effects, acts as a radiosensitizer and circumvents tumor cell-regrowth after CDDP treatment. These mechanisms may be responsible for the good clinical outcome of CapRI.

恶性肿瘤中西医结合治疗模式探索

恶性肿瘤是严重威胁人类健康的重大疾病,虽然目前中西医结合已成为我国恶性肿瘤治疗的专家共识,但尚未形成成熟的中西医结合治疗模式。通过探索构建恶性肿瘤中西医结合治疗模式,即中西医协同治疗、中医姑息治疗和中医防变治疗,覆盖恶性肿瘤不同阶段,以期在恶性肿瘤治疗过程中充分发挥中西医结合治疗的优势与特色。

聚焦超声在多模式协同治疗肝癌方面的最新研究进展

声动力疗法(Sonodynamic Therapy,SDT)是一种利用聚焦超声非入侵性治疗癌症的手段,基于SDT的协同策略治疗肝癌,具有较高的研究意义和临床转化价值。总结了SDT的治疗机理和常见声敏剂,分析了基于单模态声动力疗法很难满足现阶段治疗肝癌肿瘤原因,重点阐述声动力疗法和化疗、光动力治疗、光热治疗等双重协同治疗模式以及基于声动力的多模式协同治疗的研究进展,旨在为今后SDT协同模式治疗肝癌及其它类型癌症提供参考和借鉴,同时提出SDT协同治疗在研究过程中仍面临的单一治疗效果不显著和多模态联合治疗研究较少等问题,最后提出了开发新型声敏剂、探究联合治疗机理以及实现实时诊疗等应用等发展前景。

Injectable“cocktail”hydrogel with dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic effect

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.

新吲哚菁绿IR-820辅助的近红外荧光成像和光热及协同治疗在肿瘤诊疗中的应用进展

新吲哚菁绿IR-820因其具有强近红外(near-infrared,NIR,750~1700 nm)荧光特性、良好生物相容性、高光热转换效率及稳定性等优势,在NIR发光的有机荧光染料中脱颖而出,被广泛应用于生物医学成像、荧光标记、细胞实时监测、光热治疗等研究领域。为更好地发挥IR-820的生物医学应用价值,研究人员用不同生物化学分子修饰IR-820来增强其荧光及光热特性,制备多种类的荧光纳米粒子,在基础生物医学成像与肿瘤光热治疗方面开展了众多研究。总结了IR-820荧光纳米粒子在近红外荧光成像和通过光热机理及与其他技术协同治疗肿瘤中的应用研究,希望为进一步推进有机荧光染料IR-820在生物医学领域应用和临床转化发展提供参考。

金属有机骨架材料光热/光动力联合治疗的策略及进展

背景:金属有机骨架(metal-organic frameworks,MOFs)是一种由金属节点和有机配体组成的新型多孔材料。部分MOFs自身即具备光热转化能力或光动力效应,亦可作为载体负载光热剂或光敏剂,在激光诱导下产生活性氧或升高温度发挥光疗作用,被广泛应用于抗菌及抗肿瘤等生物医学领域。当MOFs同时具有这两种光疗作用时,可发挥协同治疗的效应,以弥补单独使用一种光疗方法的不足。目的:按照不同的结构总结目前提出的MOFs光热/光动力联合治疗策略,以期为联合治疗材料MOFs的结构设计、功能负载及临床应用场景提供新的思路。方法:以“金属有机骨架/金属有机框架,光动力治疗,光热治疗”为中文检索词,“Metal-organic frameworks,photodynamic therapy,photothermal therapy,phototherapy”为英文检索词,检索了PubMed、Web of Science、ScienceDirect、中国知网和万方数据库的文献,最终纳入76篇进行综述分析。结果与结论:①光热/光动力联合治疗可发挥相互增强的协同作用。②现有光热/光动力联合治疗策略主要包括了改性MOFs骨架赋予其光热、光动力效应,将光疗剂封装于MOFs,光疗剂与MOFs形成核壳结构,光疗剂在MOFs内原位还原,将光疗剂附着于MOFs表面以及热解MOFs以形成MOFs衍生的碳材料等其他特殊改性方法。③要构建特定的光疗MOFs结构,必须综合考虑光疗剂和MOFs的种类、尺寸、结合方式,选择不同的合成策略。封装结构合成过程简单,但仅适用于小粒径光疗剂;核壳结构稳定,但合成过程繁复;原位还原对光疗剂尺寸无特殊限制,但难以精确控制光疗剂在MOFs内部的生长;表面附着结构的合成步骤简便,但不能避免光疗剂提前聚集猝灭;热解MOFs合成条件要求高,且只有特定的MOFs才能实现。④现有的光热/光动力联合治疗策略主要被应用于抗菌、抗肿瘤治疗并表现出优异性能,具体的应用领域与光疗剂和MOFs自身的性质有关,还有部分用于类风湿性关节炎、抗凝溶栓治疗,其潜在应用场景十分广阔。⑤光热剂和光敏剂的临床转化目前仍处于起步阶段,其面临的关键挑战包括生物安全性评估激光照射参数的优化以及高效大规模合成方法的开发。

近红外光协同免疫疗法增强抗肿瘤效果研究进展

肿瘤免疫疗法虽然在一定程度上克服了传统疗法存在的复发可能性大的问题,但也存在应答率低、部分患者不良反应大的局限性.近红外光可以直接或间接激活免疫系统,且可实时成像进而监测治疗效果及评估在治疗过程中产生的不良反应,因此近红外光协同下的免疫疗法可增强抗肿瘤效果、降低各自单独使用时所引起的不良反应,是一种非常有前景的治疗方法.故对近年来近红外光协同的免疫激活治疗肿瘤的设计策略、应用、问题及对策方面进行了综述.

不同金属组成的层状双氢氧化物在医药领域的应用进展

层状双氢氧化物是由带正电的金属离子氢氧化物层和插层阴离子组成的具有二维层状结构的纳米材料,广泛用于环境治理等领域。由于制备简便、组成灵活性高、药物装载率高、pH响应型释放、生物相容性和安全性良好等特点,层状双氢氧化物逐渐在抗肿瘤治疗中崭露头角。本文综述了不同金属离子组成的层状双氢氧化物在生物医药领域中的应用进展,并对其在生物医药领域应用的进一步拓宽以及临床转化中存在的挑战进行讨论,以期对层状双氢氧化物递药系统的开发与转化提供参考。

交联诱导重组装多重刺激响应型聚合物胶束的制备及抗肿瘤应用

本工作合成了基于聚赖氨酸的三嵌段两亲性聚合物mPEG-P(LL/LL-LA)-PCL-IR820,其中聚赖氨酸链为交联剂硫辛酸(LA)提供了反应位点,疏水链段的聚己内酯(PCL)为物理包埋化疗药物阿霉素(DOX)提供了可行性。随后,光敏剂(IR820)通过酯键接枝到PCL上得到mPEG-P(LL/LL-LA)-PCL-IR820。将聚合物通过溶剂蒸发法制备未交联载药胶束(DUCM),再使用交联诱导剂二硫苏糖醇(DTT)诱导LA制备交联载药胶束(DCM)。由于内部交联结构的存在,DCM在经历注射和血液循环后保持结构稳定,并且在进入肿瘤细胞后,LA中的二硫键会在肿瘤细胞中高浓度谷胱甘肽(GSH)作用下断裂,从而释放化疗药物,避免了未交联胶束因剪切力和蛋白质吸附作用而提前裂解,进而避免了药物在体内的非特异性分布。最终,该交联纳米胶束协同化疗和光动力疗法高效杀死癌细胞,为胶束在药物传递系统中的研发提供了有价值的参考。

rNDV-IL-2和rNDV-TRAIL治疗肿瘤的协同作用

通过比较rNDV表达的白细胞介素-2(IL-2)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)治疗肿瘤的效果,并进一步探讨联合应用rNDV-IL-2和rNDV-TRAIL是否在肿瘤治疗中产生协同效应.体外培养H22肝癌细胞株和B16-F10黑色素瘤细胞株,并建立小鼠H22肝癌和B16-F10黑色素瘤动物模型,注射rNDV-IL-2和rNDV-TRAIL病毒进行治疗.同时注射人IL-2和TRAIL的重组新城疫病毒(rNDV-IL-2+rNDV-TRAIL)显著提高了rNDV通过诱导细胞凋亡来杀伤肿瘤细胞的能力.小鼠肝癌和恶性黑色素模型鼠的治疗实验表明,与对照相比,rNDV-IL-2或rNDV-TRAIL显著抑制了肿瘤的生长并延长荷瘤小鼠的存活.与rNDV-IL-2和rNDV-TRAIL治疗组相比较,rNDV-IL-2+rNDV-TRAIL联合治疗进一步增强了rNDV的抗肿瘤功效,并进一步延长了动物的存活时间.动物实验结果还表明,荷瘤鼠rNDV-IL-2和rNDV-IL-2+rNDV-TRAIL治疗后均可诱导系小鼠体内的CD4^(+)细胞和CD8^(+)细胞的增殖,并且rNDV-IL-2+rNDV-TRAIL联合治疗表现出明显的协同作用.rNDV-IL-2+rNDV-TRAIL联合治疗在体内外均能够明显抑制肿瘤增殖,较单一应用rNDV-IL-2或rNDV-TRAIL有更好的效果,值得进一步深入研究.

Near-infrared light switching nitric oxide nanogenerator with“linkage mechanism”for tumor targeting multimodal synergistic therapy

Gaseous therapy based on nitric oxide(NO),as a potential anti-tumor treatment strategy,has attracted great attention,but the targeted and controlled gas release in the tumor site still remains a challenge.In addressing these difficulties,a near-infrared(NIR)light-triggered NO release nanogenerator with a“linkage mechanism”was designed on the basis of sodium nitroprussidedoped mesoporous Prussian blue nanoparticles,in which the outer structure was modified with p H-sensitive gatekeeper chitosan and tumor-targeting agent folic acid.The“linkage mechanism”can achieve precise release of NO under the control of photothermal effect at tumor site,which can couple photothermal therapy and gas therapy to address the premature release of gas during transportation.Meanwhile,the amount of released gas can be controlled by adjusting the irradiation time and laser intensity.Furthermore,as-fabricated nanocomposites hold high photothermal conversion efficiency under NIR laser irradiation,resulting in the on-demand release of NO and chemotherapy drugs.The released NO can inhibit the expression of hypoxiainducible factorα(HIF-1α)and alleviate the hypoxic tumor microenvironment,thereby enhancing the efficacy of chemotherapy.Moreover,in vitro and in vivo experiments exhibited remarkable antitumor efficiency,and the synergistic gas/chemo/photothermal therapy of deep tumors was achieved.These findings indicate an effective strategy to stimulate further the development of deep tumor therapy,which may provide new insights into other NO-related medical applications.

Carbon dots with two-photon fluorescence imaging for efficient synergistic trimodal therapy

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.