Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and en...Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma.By an ingenious design,the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization.After G2 dendrimer decoration,the overall charge is changed from neutral to positive,and the NGs-G2 display the whole charge nature of positively charged corona and neutral core.Importantly,the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo.As a consequence of this alteration,the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation,enhanced tumor uptake,and promoted drug release,resulting in the significantly augmented antitumor efficacy with low side effects.Remarkably,this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake.Moreover,the NGs-G2 also displayed thermal/pH dual-responsive behaviors,excellent biocompatibility,improved cellular uptake,and stimuli-responsive drug release.Encouragingly,this work demonstrates a novel insight into the strategy for optimizing design,improving biodistribution and enhancing theranostic efficacy of nanocarriers.展开更多
For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs...For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented chemotherapy.CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method.The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic pH.The R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading efficiency.Encouragingly,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo.Notably,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported elsewhere.The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.展开更多
基金This research was financially supported by the Sino-German Center for Research Promotion(GZ1505),DFG(SFB 985,Functional Microgels and Microgel Systems),National Natural Science Foundation of China(81801704 and 81761148028)Science and Technology Commission of Shanghai Municipality(18520750400)Shanghai Sailing Program(18YF1415300)。
文摘Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma.By an ingenious design,the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization.After G2 dendrimer decoration,the overall charge is changed from neutral to positive,and the NGs-G2 display the whole charge nature of positively charged corona and neutral core.Importantly,the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo.As a consequence of this alteration,the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation,enhanced tumor uptake,and promoted drug release,resulting in the significantly augmented antitumor efficacy with low side effects.Remarkably,this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake.Moreover,the NGs-G2 also displayed thermal/pH dual-responsive behaviors,excellent biocompatibility,improved cellular uptake,and stimuli-responsive drug release.Encouragingly,this work demonstrates a novel insight into the strategy for optimizing design,improving biodistribution and enhancing theranostic efficacy of nanocarriers.
基金This research was financially supported by the Sino-German Center for Research Promotion(GZ1505)National Natural Science Foundation of China(81801704 and 81761148028)+5 种基金the Science and Technology Commission of Shanghai Municipality(19XD1400100)Shanghai Sailing Program(18YF1415300)the China Scholarship Council(for X.Li)X.Shi also thanks the support by FCT-Fundaçao para a Ciencia e a Tecnologia through the CQM Base Fund-UIDB/00674/2020Programmatic Fund-UIDP/00674/2020by ARDITI-Agencia Regional para o Desenvolvimento da Investigaçao Tecnologia e Inovaçao,through the project M1420-01-0145-FEDER-000005-Centro de Química da Madeira-CQM+(Madeira 14-20 Program).
文摘For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented chemotherapy.CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method.The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic pH.The R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading efficiency.Encouragingly,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo.Notably,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported elsewhere.The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.
