How to fabricate zeolitic imidazole framework-8 （ZIF-8） based therapeutic nanoplatform will be of significance in biomedicine considering its good biocompatibility. Herein, we report a one-step encapsulation of indo...How to fabricate zeolitic imidazole framework-8 （ZIF-8） based therapeutic nanoplatform will be of significance in biomedicine considering its good biocompatibility. Herein, we report a one-step encapsulation of indocyanine green （ICG） in ZlF-8 nanoparticles （NPs）. The as-prepared ICG@ZIF-8 NPs possess an absorption band in the near infrared region and have the good photothermal conversion efficiency. The in vivo and in vitro studies show that, after loading chemotherapy agent hydrophobic doxorubicin （DOX）, ICG@ZIF-8-DOX NPs exhibit the chem-and photothermal synergistic therapy for tumor. In addition, it is found that the embedded ICG molecules in ICG@ZlF-8 NPs can be disassociated and released into the solution upon the 808 nm laser irradiation, demonstrating that as-prepared ICG@ZIF-8 NPs can also be used as the optical imaging probe to trace the degradability behavior of resulting NPs in future展开更多
diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance im...diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.展开更多
Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable...Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology.Here,a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics.Multiple interaction forces are found to drive the co-assembly process.Moreover,DOX release from the nanoassembly can bewell controlled by the acidic tumormicroenvironment and laser irradiation,resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo.As expected,the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells(4T1)on BALB/c mice,owing to synergistic chemo-photothermal therapy.More interestingly,DiR and DOX synergistically induce immunogenic cell death(ICD)of tumor cells after treatment,enabling the mice to acquire immune memory against tumor growth and recurrence.Such a facile nanoassembly technique provides a novelmultimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.展开更多
The design and synthesis of multifunctional nanocarriers for efficient synergistic cancer therapy have drawn great research interests in recent years.In this work,a nanoplatform for chemo-photothermal therapy with tar...The design and synthesis of multifunctional nanocarriers for efficient synergistic cancer therapy have drawn great research interests in recent years.In this work,a nanoplatform for chemo-photothermal therapy with targeting ligand was developed.Hollow porous structured silica nanotubes(SNTs)with controllable lengths decorated with CuS nanoparticles(NPs)on the surface as photothermal agents were prepared and further conjugated with lactobionic acid groups as a cancer cell target.SNTs with average lengths of 40,55 and 150 nm were obtained and further functionalized as drug carriers.The smallest bifunctional SNTs with targeting groups show good biocompatibility and highest cellular uptake for HepG2 cells.The release of doxorubicin hydrochloride(DOX)from the SNTs was dependent on the p H of the buffer solution and 808-nm near infrared(NIR)light irradiation.The integration of photothermal therapy(PTT)of CuS NPs and chemotherapy of anticancer drug leads to a better tumor inhibition effect than the individual therapy alone in vitro and in vivo.These results demonstrate potential applications of the nanocomposites as vector for efficient chemo-photothermal therapy.展开更多
Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep...Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.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
Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency.Herein,we constructed a nanocomposite based on gold nanorods(GNRs)and drug-loaded tetrahedral DNA nanostruct...Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency.Herein,we constructed a nanocomposite based on gold nanorods(GNRs)and drug-loaded tetrahedral DNA nanostructures(TDN)for chemophotothermal combinational therapy.Anti-tumor drug doxorubicin(DOX)was loaded via the insertion within GC base pairs of TDN.The aptamer AS1411 was attached to the apex of TDN(ATDN)to target tumor cells.The DOX-loaded DNA tetrahedron(ATDN-DOX)was compressed by the GNRs coated with PEI(GNRs@ATDN-DOX)to realize the photothermal function and lysosome escape.GNRs under the illumination of 808nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer.The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN.The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape.The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.展开更多
Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy.However,traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving phototherma...Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy.However,traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving photothermal properties,as it results in complicated synthesis process,inefficient photothermal effects and hindered NIR-mediated drug release.Herein we report a facile synthesis of a polyethylene glycol(PEG)linked liposome(PEG-liposomes)coated doxorubicin(DOX)-loaded ordered mesoporous carbon(OMC)nanocomponents(PEG-LIP@OMC/DOX)by simply sonicating DOX and OMC in PEG-liposomes suspensions.The as-obtained PEG-LIP@OMC/DOX exhibits a nanoscale size(600±15 nm),a negative surface potential(-36.70 mV),high drug loading(131.590 mg/g OMC),and excellent photothermal properties.The PEG-LIP@OMC/DOX can deliver loaded DOX to human MCF-7 breast cancer cells(MCF-7)and the cell toxicity viability shows that DOX unloaded PEG-LIP@OMC has no cytotoxicity,confirming the PEG-LIP@OMC itself has excellent biocompatibility.The NIR-triggered release studies demonstrate that this NIR-responsive drug delivery system enables on-demand drug release.Furthermore,cell viability results using human MCF-7 cells demonstrated that the combination of NIR-based hyperthermal therapy and triggered chemothe rapy can provide higher therapeutic efficacy than re spective monothe rapies.With these excellent features,we believe that this phospholipid coating based multifunctional delivery system strategy should promote the application of OMC in nanomedical applications.展开更多
Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in...Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy.Herein,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging.The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)irradiation.This study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site.Moreover,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment.Overall,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.展开更多
Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Her...Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.展开更多
Pt(Ⅱ)-based metallacycles,as an important family of supramolecular coordination complexes(SCCs),have exhibited excellent antitumor activity at the cell level.However,the biomedical applications of Pt(Ⅱ)-based metall...Pt(Ⅱ)-based metallacycles,as an important family of supramolecular coordination complexes(SCCs),have exhibited excellent antitumor activity at the cell level.However,the biomedical applications of Pt(Ⅱ)-based metallacycles for animal studies are still hindered by their poor stability,non-targeted tumour,and lack of detectable feedback for evaluating therapeutic progress.Herein,we propose a strategy that introduces melanin dots as a biomedical platform to load bright-emission Pt(Ⅱ)-based metallacycles,thereby constructing a theranostic agent that enables photoacoustic imaging(PAI)-guided chemo-photothermal combinational therapy.Melanin dots act as a protective carrier to preserve the integrity of Pt(Ⅱ)-based metallacycles before uptake by tumour tissues.Meanwhile,the PAI signal from melanin dots furnishes more comprehensive information on the tumour.Moreover,the heat generated after NIR laser irradiation can not only trigger the apoptosis of tumour cells but also promote the deeper penetration of Pt(Ⅱ)-based SCCs into tumour tissue,thus enhancing the efficiency of chemotherapy.展开更多
Developing low toxicity and multifunctional theranostic nanoplatform is the key for precise cancer diagnosis and treatment.Herein,an inorganic-organic hybrid nanocomposite is designed by modifying zirconium dioxide(Zr...Developing low toxicity and multifunctional theranostic nanoplatform is the key for precise cancer diagnosis and treatment.Herein,an inorganic-organic hybrid nanocomposite is designed by modifying zirconium dioxide(ZrO_(2)) with polydopamine(PDA) followed by doping Mn^(2+) ions and functionalizing with Tween 20(Tween-ZrO_(2)@PDA-Mn2+) for multimodal imaging and chemo-photothermal combination therapy.The as-prepared nanocomposite exhibits good biocompatibility in vitro and in vivo.Specifically,it can be employed as a multifunctional platform not only for computed tomography(CT)imaging and T1-weighted magnetic resonance(MR) imaging,but also for efficient chemotherapeutic drug doxorubicin hydrochloride(DOX) loading.Importantly,because of the pronounced photothermal conversion performance and controllable DOX release ability triggered by the near-infrared(NIR)irradiation and acidic pH,the synergistic effect between photothermal the rapy and chemotherapy results in an enhanced cancer treatment efficacy in vivo.Our work provides a high-performance inorganicorganic hybrid nanotheranostic platform for chemo-photothermal cancer therapy guided by CT and MR imaging.展开更多
In recent years,synergistic chemo-photothermal therapy has revealed promising potential in treatments against various kinds of cancer.However,the development of superb photothermal agents with high drug loading capaci...In recent years,synergistic chemo-photothermal therapy has revealed promising potential in treatments against various kinds of cancer.However,the development of superb photothermal agents with high drug loading capacity is still highly required.In this work,a hollow mesoporous polyaniline nanoparticle(HPANI NP)has been developed for encapsulating chemotherapeutic drug doxorubicin(DOX)with an remarkable drug loading content as high as 37.5%.Additional PEG modification endowed the drugloaded HPANI NPs with improved water-dispersibility and bioavailability.Such PEG-HPANI-DOX NPs exhibited strong NIR absorbance and robust photothermal conversion capacity,exhibiting highly efficient synergistic cancer treatment.More interestingly,the responsively released DOX molecules could emit strong red fluorescence,which could be employed to monitor the cellular endocytosis and drug release profile of PEG-HPANI-DOX NPs.Finally,the as-fabricated NPs showed good biocompatibility and low toxicity,serving as a promising nanoagent for highly efficient drug delivery and cancer combination therapy.展开更多
目的 为了实现光热化疗联合治疗,提高抗肿瘤效果,将具有抗肿瘤作用的β-榄香烯(β-elemene,Ele)装载于聚乳酸羟基乙酸共聚物[poly(D,L-lactide-co-glycolic acid),PLGA]纳米粒(Ele-PLGA NPs)中,并在载药纳米粒表面进一步包覆了聚单宁酸(...目的 为了实现光热化疗联合治疗,提高抗肿瘤效果,将具有抗肿瘤作用的β-榄香烯(β-elemene,Ele)装载于聚乳酸羟基乙酸共聚物[poly(D,L-lactide-co-glycolic acid),PLGA]纳米粒(Ele-PLGA NPs)中,并在载药纳米粒表面进一步包覆了聚单宁酸(poly-tannic acid,pTA),制得Ele-PLGA-pTA纳米粒(Ele-PLGA-p TA NPs)。方法 首先利用O/W乳化法制备Ele-PLGA NPs,然后加入单宁酸与Fe3+发生络合反应,形成pTA分子层附着在Ele-PLGA NPs表面,最终形成ElePLGA-p TA NPs,通过马尔文激光粒度仪和透射电子显微镜对该系统的粒径、ζ电位、稳定性以及粒子形态进行考察;分别利用HPLC法和BCA试剂盒对β-榄香烯的载药量和单宁酸的包覆率进行测定;通过红外热成像仪评价PLGA-p TA NPs的光热升温效率和光热稳定性;通过MTT法考察载药纳米粒对Lewis肺癌细胞(Lewis lung cancer cell,LLC)的细胞毒性;通过建立小鼠LLC皮下肿瘤模型对Ele-PLGA-p TA NPs的体内光热-化疗联合抗肿瘤效果进行探究。结果 经测定,Ele-PLGAp TA NPs对β-榄香烯的载药量和单宁酸的包覆率分别为(6.6±0.1)%、(5.4±0.1)%。其形态呈球形,粒径为(202.9±2.7)nm,ζ电位为(-37.5±0.2)m V,分散性良好。体外光热性能考察结果表明,在近红外激光(NIR laser)的照射下,PLGAp TA NPs表现出良好的光热转换能力和光热稳定性。体外细胞实验结果表明,空白载体组(PLGA-pTA NPs)基本没有细胞毒性,与单一化疗组(Ele-PLGA-p TA NPs)相比,光热-化疗联合组(Ele-PLGA-p TA NPs+Laser)具有更强的细胞毒性。体内实验结果表明,与单纯光热治疗组(PLGA-p TA NPs+Laser)和单一化疗组(Ele-PLGA-pTA NPs)对照组相比,光热-化疗联合组(Ele-PLGA-p TA NPs+Laser)对小鼠肿瘤生长的抑制效果最为显著(P<0.001)。结论 所制备的Ele-PLGA-p TA NPs能够实现光热-化疗联合治疗,显著提高抗肿瘤效果。展开更多
基金financially supported by the State Key Basic Research Program of the PRC(No.2014CB744501)the NSF of China(No.81771976)+1 种基金Fundamental Research Funds for the Central Universitiesthe joint fund of Southeast University and Nanjing Medical University
文摘How to fabricate zeolitic imidazole framework-8 （ZIF-8） based therapeutic nanoplatform will be of significance in biomedicine considering its good biocompatibility. Herein, we report a one-step encapsulation of indocyanine green （ICG） in ZlF-8 nanoparticles （NPs）. The as-prepared ICG@ZIF-8 NPs possess an absorption band in the near infrared region and have the good photothermal conversion efficiency. The in vivo and in vitro studies show that, after loading chemotherapy agent hydrophobic doxorubicin （DOX）, ICG@ZIF-8-DOX NPs exhibit the chem-and photothermal synergistic therapy for tumor. In addition, it is found that the embedded ICG molecules in ICG@ZlF-8 NPs can be disassociated and released into the solution upon the 808 nm laser irradiation, demonstrating that as-prepared ICG@ZIF-8 NPs can also be used as the optical imaging probe to trace the degradability behavior of resulting NPs in future
基金supported by Institute of Nanomaterials and Nanotechnology,Lishui Hospital of Zhejiang UniversityPostdoctoral Foundation of ZheJiang province+2 种基金National Key Research and Development projects intergovernmental cooperation in science and technology of China(2018YFE0126900)Zhejiang Provincial Natural Science Foundation(LY15H030010,LY20H180016,Q21H180011)The Key R&D Program of Lishui City(2019ZDYF17).
文摘diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.
基金financially supported by the Liaoning Revitalization Talents Program (no. XLYC1907129)the National Natural Science Foundation of China (no. 82161138029)+1 种基金the Excellent Youth Science Foundation of Liaoning Province (no. 2020-YQ-06)the China Postdoctoral Science Foundation (no. 2020M670794 and no. 2021MD703858)
文摘Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology.Here,a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics.Multiple interaction forces are found to drive the co-assembly process.Moreover,DOX release from the nanoassembly can bewell controlled by the acidic tumormicroenvironment and laser irradiation,resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo.As expected,the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells(4T1)on BALB/c mice,owing to synergistic chemo-photothermal therapy.More interestingly,DiR and DOX synergistically induce immunogenic cell death(ICD)of tumor cells after treatment,enabling the mice to acquire immune memory against tumor growth and recurrence.Such a facile nanoassembly technique provides a novelmultimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.
基金supported by the National Natural Science Foundation of China(NSFC,51572257,51720105015,51672269,51929201,51922097,51772124 and 51872282)the Science and Technology Cooperation Project between Chinese and Australian Governments(2017YFE0132300)+4 种基金the Key Research Program of Frontier Sciences,CAS(YZDY-SSW-JSC018)the Overseas,Hong Kong&Macao Scholars Collaborated Researching Fund(21728101)the CAS-Croucher Funding Scheme for Joint Laboratories(CAS18204)Jiangmen Innovative Research Team Program(2017)the Major Program of Basic Research and Applied Research of Guangdong Province(2017KZDXM083)。
文摘The design and synthesis of multifunctional nanocarriers for efficient synergistic cancer therapy have drawn great research interests in recent years.In this work,a nanoplatform for chemo-photothermal therapy with targeting ligand was developed.Hollow porous structured silica nanotubes(SNTs)with controllable lengths decorated with CuS nanoparticles(NPs)on the surface as photothermal agents were prepared and further conjugated with lactobionic acid groups as a cancer cell target.SNTs with average lengths of 40,55 and 150 nm were obtained and further functionalized as drug carriers.The smallest bifunctional SNTs with targeting groups show good biocompatibility and highest cellular uptake for HepG2 cells.The release of doxorubicin hydrochloride(DOX)from the SNTs was dependent on the p H of the buffer solution and 808-nm near infrared(NIR)light irradiation.The integration of photothermal therapy(PTT)of CuS NPs and chemotherapy of anticancer drug leads to a better tumor inhibition effect than the individual therapy alone in vitro and in vivo.These results demonstrate potential applications of the nanocomposites as vector for efficient chemo-photothermal therapy.
基金the National Natural Science Foundation of China(No.81803466)the Key Areas Research and Development Program of Guangdong Province(No.2019B020204002)the Natural Science Foundation of Guangdong Province(No.2021A1515012525).
文摘Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.
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supported by the National Natural Science Foundation of China(51873121).
文摘Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency.Herein,we constructed a nanocomposite based on gold nanorods(GNRs)and drug-loaded tetrahedral DNA nanostructures(TDN)for chemophotothermal combinational therapy.Anti-tumor drug doxorubicin(DOX)was loaded via the insertion within GC base pairs of TDN.The aptamer AS1411 was attached to the apex of TDN(ATDN)to target tumor cells.The DOX-loaded DNA tetrahedron(ATDN-DOX)was compressed by the GNRs coated with PEI(GNRs@ATDN-DOX)to realize the photothermal function and lysosome escape.GNRs under the illumination of 808nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer.The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN.The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape.The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.
基金the National Natural Science Foundation of China(Nos.21735002,21521063,21675046,21874035,21806186 and 21775036)the Natural Science Foundation of Hunan Province,China(No.2018JJ2033)the Key Point Research and Invention Program of Hunan Province,China(No.2017DK2011)。
文摘Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy.However,traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving photothermal properties,as it results in complicated synthesis process,inefficient photothermal effects and hindered NIR-mediated drug release.Herein we report a facile synthesis of a polyethylene glycol(PEG)linked liposome(PEG-liposomes)coated doxorubicin(DOX)-loaded ordered mesoporous carbon(OMC)nanocomponents(PEG-LIP@OMC/DOX)by simply sonicating DOX and OMC in PEG-liposomes suspensions.The as-obtained PEG-LIP@OMC/DOX exhibits a nanoscale size(600±15 nm),a negative surface potential(-36.70 mV),high drug loading(131.590 mg/g OMC),and excellent photothermal properties.The PEG-LIP@OMC/DOX can deliver loaded DOX to human MCF-7 breast cancer cells(MCF-7)and the cell toxicity viability shows that DOX unloaded PEG-LIP@OMC has no cytotoxicity,confirming the PEG-LIP@OMC itself has excellent biocompatibility.The NIR-triggered release studies demonstrate that this NIR-responsive drug delivery system enables on-demand drug release.Furthermore,cell viability results using human MCF-7 cells demonstrated that the combination of NIR-based hyperthermal therapy and triggered chemothe rapy can provide higher therapeutic efficacy than re spective monothe rapies.With these excellent features,we believe that this phospholipid coating based multifunctional delivery system strategy should promote the application of OMC in nanomedical applications.
基金National Key Research and Development projects intergovernmental cooperation in science and technology of China(No.2018YFE0126900)Zhejiang Provincial Natural Science Foundation(Nos.LD21H300002,LY18H180005,and LQ21H180003).
文摘Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy.Herein,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging.The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)irradiation.This study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site.Moreover,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment.Overall,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.
基金financially supported by the National Natural Science Foundation of China (Nos.31771036,51703132)the Basic Research Program of Shenzhen (Nos.JCYJ20180507182413022,JCYJ20170412111100742)the Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (No.2018B030308003)。
文摘Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.
基金the National Key Research and Development Program(2017YFA0505203)the National Natural Science Foundation of China(21672070)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Opening Projects of Shanghai Key Laboratory of Green Chemistry and Chemical Processes。
文摘Pt(Ⅱ)-based metallacycles,as an important family of supramolecular coordination complexes(SCCs),have exhibited excellent antitumor activity at the cell level.However,the biomedical applications of Pt(Ⅱ)-based metallacycles for animal studies are still hindered by their poor stability,non-targeted tumour,and lack of detectable feedback for evaluating therapeutic progress.Herein,we propose a strategy that introduces melanin dots as a biomedical platform to load bright-emission Pt(Ⅱ)-based metallacycles,thereby constructing a theranostic agent that enables photoacoustic imaging(PAI)-guided chemo-photothermal combinational therapy.Melanin dots act as a protective carrier to preserve the integrity of Pt(Ⅱ)-based metallacycles before uptake by tumour tissues.Meanwhile,the PAI signal from melanin dots furnishes more comprehensive information on the tumour.Moreover,the heat generated after NIR laser irradiation can not only trigger the apoptosis of tumour cells but also promote the deeper penetration of Pt(Ⅱ)-based SCCs into tumour tissue,thus enhancing the efficiency of chemotherapy.
基金supported by the National Natural Science Foundation of China (Nos.51772293,U1932112,and 21471103)Beijing Natural Science Foundation (No.2202064)+1 种基金Science and Technology Innovation Service Ability Construction Project of the Beijing Municipal Commission of Education (No.19530050182)CAS Key Laboratory of Nano-Bio Interface (No.20NBI01)。
文摘Developing low toxicity and multifunctional theranostic nanoplatform is the key for precise cancer diagnosis and treatment.Herein,an inorganic-organic hybrid nanocomposite is designed by modifying zirconium dioxide(ZrO_(2)) with polydopamine(PDA) followed by doping Mn^(2+) ions and functionalizing with Tween 20(Tween-ZrO_(2)@PDA-Mn2+) for multimodal imaging and chemo-photothermal combination therapy.The as-prepared nanocomposite exhibits good biocompatibility in vitro and in vivo.Specifically,it can be employed as a multifunctional platform not only for computed tomography(CT)imaging and T1-weighted magnetic resonance(MR) imaging,but also for efficient chemotherapeutic drug doxorubicin hydrochloride(DOX) loading.Importantly,because of the pronounced photothermal conversion performance and controllable DOX release ability triggered by the near-infrared(NIR)irradiation and acidic pH,the synergistic effect between photothermal the rapy and chemotherapy results in an enhanced cancer treatment efficacy in vivo.Our work provides a high-performance inorganicorganic hybrid nanotheranostic platform for chemo-photothermal cancer therapy guided by CT and MR imaging.
基金financial support by the National Natural Science Foundation of China(32001010 and 21701018)Beijing Natural Science Foundation(2214078)+1 种基金Beijing Institute of Technology Research Fund Program for Young ScholarsThe Young Elite Scientist Sponsorship Program of Beijing Association for Science and Technology(2021–2023)。
文摘In recent years,synergistic chemo-photothermal therapy has revealed promising potential in treatments against various kinds of cancer.However,the development of superb photothermal agents with high drug loading capacity is still highly required.In this work,a hollow mesoporous polyaniline nanoparticle(HPANI NP)has been developed for encapsulating chemotherapeutic drug doxorubicin(DOX)with an remarkable drug loading content as high as 37.5%.Additional PEG modification endowed the drugloaded HPANI NPs with improved water-dispersibility and bioavailability.Such PEG-HPANI-DOX NPs exhibited strong NIR absorbance and robust photothermal conversion capacity,exhibiting highly efficient synergistic cancer treatment.More interestingly,the responsively released DOX molecules could emit strong red fluorescence,which could be employed to monitor the cellular endocytosis and drug release profile of PEG-HPANI-DOX NPs.Finally,the as-fabricated NPs showed good biocompatibility and low toxicity,serving as a promising nanoagent for highly efficient drug delivery and cancer combination therapy.
文摘目的 为了实现光热化疗联合治疗,提高抗肿瘤效果,将具有抗肿瘤作用的β-榄香烯(β-elemene,Ele)装载于聚乳酸羟基乙酸共聚物[poly(D,L-lactide-co-glycolic acid),PLGA]纳米粒(Ele-PLGA NPs)中,并在载药纳米粒表面进一步包覆了聚单宁酸(poly-tannic acid,pTA),制得Ele-PLGA-pTA纳米粒(Ele-PLGA-p TA NPs)。方法 首先利用O/W乳化法制备Ele-PLGA NPs,然后加入单宁酸与Fe3+发生络合反应,形成pTA分子层附着在Ele-PLGA NPs表面,最终形成ElePLGA-p TA NPs,通过马尔文激光粒度仪和透射电子显微镜对该系统的粒径、ζ电位、稳定性以及粒子形态进行考察;分别利用HPLC法和BCA试剂盒对β-榄香烯的载药量和单宁酸的包覆率进行测定;通过红外热成像仪评价PLGA-p TA NPs的光热升温效率和光热稳定性;通过MTT法考察载药纳米粒对Lewis肺癌细胞(Lewis lung cancer cell,LLC)的细胞毒性;通过建立小鼠LLC皮下肿瘤模型对Ele-PLGA-p TA NPs的体内光热-化疗联合抗肿瘤效果进行探究。结果 经测定,Ele-PLGAp TA NPs对β-榄香烯的载药量和单宁酸的包覆率分别为(6.6±0.1)%、(5.4±0.1)%。其形态呈球形,粒径为(202.9±2.7)nm,ζ电位为(-37.5±0.2)m V,分散性良好。体外光热性能考察结果表明,在近红外激光(NIR laser)的照射下,PLGAp TA NPs表现出良好的光热转换能力和光热稳定性。体外细胞实验结果表明,空白载体组(PLGA-pTA NPs)基本没有细胞毒性,与单一化疗组(Ele-PLGA-p TA NPs)相比,光热-化疗联合组(Ele-PLGA-p TA NPs+Laser)具有更强的细胞毒性。体内实验结果表明,与单纯光热治疗组(PLGA-p TA NPs+Laser)和单一化疗组(Ele-PLGA-pTA NPs)对照组相比,光热-化疗联合组(Ele-PLGA-p TA NPs+Laser)对小鼠肿瘤生长的抑制效果最为显著(P<0.001)。结论 所制备的Ele-PLGA-p TA NPs能够实现光热-化疗联合治疗,显著提高抗肿瘤效果。
