Preparation and anti-tumor application of hyaluronic acid-based material for disulfide and copper ions co-delivery

查看全文 作　　者：PANG [1]Long;ZHONG [1]Wei;WANG [1]QiuBo;FENG [1]HaoHui;DONG [1]HaoNan;WANG [1]Song;CONG [1,2]HaiLin;SHEN [1,3]YouQing;YU [1,2]Bing 机构地区：[1]Institute of Biomedical Materials and Engineering,College of Chemistry and Chemical Engineering,College of Materials Science and Engineering,Affiliated Hospital of Qingdao University,Qingdao University,Qingdao 266071,China;[2]State Key Laboratory of Bio-Fibers and Eco-Textiles,Qingdao University,Qingdao 266071,China;[3]Key Laboratory of Biomass Chemical Engineering of Ministry of Education,Center for Bionanoengineering,Department of Chemical and Biological Engineering,Zhejiang University,Hangzhou,310027,China 出　　处：《Science China(Technological Sciences)》索引2021年第64卷第9期,共10页 基　　金：This work was supported by the National Natural Science Foundation of China(Grant Nos.21675091,21874078 and 22074072);the Taishan Young Scholar Program of Shandong Province(Grant No.tsqn20161027);the Natural Science Foundation of Shandong Province(Grant No.ZR2019BEM009);the Major Science and Technology Innovation Project of Shandong Province(Grant No.2018CXGC1407);the Key Research and Development Project of Shandong Province(Grant Nos.2016GGX102028,2016GGX102039 and 2017GGX20111);the Innovation Leader Project of Qingdao(Grant No.168325zhc);the Postdoctoral Scientific Research Foundation of Qingdao(Grant No.40518060004);the First Class Discipline Project of Shandong Province。 摘　　要：Disulfide(DSF) has been proved good anti-tumor effect and even better with coadministration of Cu^(2+). In this work, we report the use of hyaluronic acid(HA) based materials to construct vectors for the delivery of both DSF and Cu^(2+). HA was firstly modified with polyethylene glycol monomethyl ether(mPEG) and polycaprolactone(PCL) to synthesize an amphiphilic polymer(HA-PEG-PCL). DSF could be loaded in the hydrophobic core and Cu^(2+) could be cooperated to the negative hydrophilic segment. The Cu^(2+) also played a role as crosslinking agent, which prevented DSF leakage prematurely, avoiding the bad side effects to normal tissues. The interaction between HA and CD44 improved the distribution of nanodrugs in tumor cells. When the nanodrugs were delivered to the cancer cell, the acidic micro-environment would separate the Cu^(2+) from the surface, leading to the disintegration of the micelles, promoting the release of DSF from the micelle core. The results of in vitro and in vivo experiments showed that the DSF and Cu^(2+) co-delivery vector constructed in this work could enhance the antitumor effect and have low biological toxicity. 关 键 词：hyaluronic acid DISULFIDE Cu^(2+) CANCER CO-DELIVERY