Though the development of the diverse hypoxia-activated prodrugs(HAPs)has made great progresses in the last several decades,current cancer therapy based on HAPs still suffers many obstacles,e.g.,poor therapeutic outco...Though the development of the diverse hypoxia-activated prodrugs(HAPs)has made great progresses in the last several decades,current cancer therapy based on HAPs still suffers many obstacles,e.g.,poor therapeutic outcome owing to hard deep reaching to hypoxic region,and the occurrence of metastasis due to hypoxia.Inspired by engineered niches,a novel functional chitosan polymer(CS-FTP)is synthesized for construction of a hydrogel-based bio-niche(CS-FTP-gel)in aiming at remodeling tumor hypoxic microenvironment.The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor,in which a HAP(i.e.,AQ4N)could be physically encapsulated,resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy.Furthermore,Pazopanib(PAZ)conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation,eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model.This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.展开更多
Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis.In this study, we prepared mu...Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis.In this study, we prepared multifunctional microspheres loading ^(131)I-labeled hollow copper sulfide nanoparticles and paclitaxel( ^(131)I-HCu SNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats.18 F-fluordeoxyglucose(18 F-FDG) positron emission tomography/computed tomography(PET/CT) imaging detected that the expansion of the tumor volume was delayed(Po0.05) following intra-tumoral(i.t.) injection with ^(131)I-HCu SNPs-MS-PTX plus near-infrared(NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography(SPECT)/photoacoustic imaging mediated by ^(131)I-HCu SNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that ^(131)I-HCu SNPs-MS-PTX offered combined photothermal, chemo-and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, ^(131)I-HCu SNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.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
基金National Key Research and Development Program of China(Grant No.2021YFB3801001)National Natural Science Foundation of China(Grant Nos.32030061)+2 种基金Key Program for Basic Research of Shanghai(Grant No.19JC1415600,21JC1406000)All the animal experiments were performed with the approval of the Fudan University Experimental Animal Centeranimal biomedical research authorization numbered is 2020-Cancer hospital-JS220.
文摘Though the development of the diverse hypoxia-activated prodrugs(HAPs)has made great progresses in the last several decades,current cancer therapy based on HAPs still suffers many obstacles,e.g.,poor therapeutic outcome owing to hard deep reaching to hypoxic region,and the occurrence of metastasis due to hypoxia.Inspired by engineered niches,a novel functional chitosan polymer(CS-FTP)is synthesized for construction of a hydrogel-based bio-niche(CS-FTP-gel)in aiming at remodeling tumor hypoxic microenvironment.The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor,in which a HAP(i.e.,AQ4N)could be physically encapsulated,resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy.Furthermore,Pazopanib(PAZ)conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation,eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model.This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.
基金partially supported by National Natural Science Foundation of China (Nos. 81771861, 81471708, 81673018, 81530053, 81471685)the award of the "National Youth Thousand Talents Plan" of China, the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (No. 2012-05)+2 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No. 20172010)2018 Shanghai Scientific and Technological Innovation Program(No. 18410711200)the Ph.D. Innovation Fund of Shanghai Jiao Tong University, School of Medicine (BXJ201821)
文摘Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis.In this study, we prepared multifunctional microspheres loading ^(131)I-labeled hollow copper sulfide nanoparticles and paclitaxel( ^(131)I-HCu SNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats.18 F-fluordeoxyglucose(18 F-FDG) positron emission tomography/computed tomography(PET/CT) imaging detected that the expansion of the tumor volume was delayed(Po0.05) following intra-tumoral(i.t.) injection with ^(131)I-HCu SNPs-MS-PTX plus near-infrared(NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography(SPECT)/photoacoustic imaging mediated by ^(131)I-HCu SNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that ^(131)I-HCu SNPs-MS-PTX offered combined photothermal, chemo-and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, ^(131)I-HCu SNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.
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.