Intelligent nanogels with self-adaptive responsiveness for improved tumor drug delivery and augmented chemotherapy  

作　　者：Xin Li Helin Li Changchang Zhang Andrij Pich Lingxi Xing Xiangyang Shi 

机构地区：[1]Department of Gynecology and Obstetrics,XinHua Hospital Affiliated to Shanghai JiaoTong University School of Medicine,Shanghai,200092,China [2]DWI-Leibniz-Institute for Interactive Materials e.V.,52056,Aachen,Germany [3]College of Chemistry,Chemical Engineering and Biotechnology,Donghua University,Shanghai,201620,China [4]Institute for Technical and Macromolecular Chemistry,RWTH Aachen University,52074,Aachen,Germany [5]CQM-Centro de Química da Madeira,Universidade da Madeira,Campus da Penteada,9000-390,Funchal,Portugal [6]Aachen Maastricht Institute for Biobased Materials,Maastricht University,6167,RD Geleen,Netherlands

出　　处：《Bioactive Materials》2021年第10期3473-3484,共12页生物活性材料（英文）

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);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/00674/2020;Programmatic Fund-UIDP/00674/2020;by 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).

摘　　要：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.

关 键 词：Ultrafast charge conversion NANOGELS Active transportation Deep tumor penetration Enhanced antitumor activity 

分 类 号：R318.08[医药卫生—生物医学工程] R73[医药卫生—基础医学]