Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine  

作　　者：Ying Wang Di Gao Yan Liu Xiaoqing Guo Shuojia Chen Li Zeng Jinxuan Ma Xingcai Zhang Zhongmin Tian Zhe Yang 

机构地区：[1]The Key Laboratory of Biomedical Information Engineering of Ministry of Education,School of Life Science and Technology,Xi’an Jiaotong University,Xi’an,710049,China [2]John A.Paulson School of Engineering and Applied Sciences,Harvard University,Cambridge,MA,02138,United States [3]School of Engineering,Massachusetts Institute of Technology,Cambridge,MA,02139,United States

出　　处：《Bioactive Materials》2021年第6期1513-1527,共15页生物活性材料（英文）

基　　金：This research was supported by the National Natural Science Foundation of China(51703178,51903203,81770728);the China Postdoctoral Science Foundation(2019M663742,2019M653661);Natural Science Foundation of Zhejiang Province(LWY20H180002).

摘　　要：Combining chemo-therapeutics with immune checkpoint inhibitors facilitates killing cancer cells and activating the immune system through inhibiting immune escape.However,their treatment effects remain limited due to the compromised accumulation of both drugs and inhibitors in certain tumor tissues.Herein,a new poly(acrylamide-co-acrylonitrile-co-vinylimidazole-co-bis(2-methacryloyl)oxyethyl disulfide)(PAAVB)polymer-based intelligent platform with controllable upper critical solution temperature(UCST)was used for the simultaneous delivery of paclitaxel(PTX)and curcumin(CUR).Additionally,a hyaluronic acid(HA)layer was coated on the surface of PAAVB NPs to target the CD44-overexpressed tumor cells.The proposed nanomedicine demonstrated a gratifying accumulation in tumor tissue and uptake by cancer cells.Then,the acidic microenvironment and high level of glutathione(GSH)in cancer cells could spontaneously decrease the UCST of polymer,leading to the disassembly of the NPs and rapid drug release at body temperature without extra-stimuli.Significantly,the released PTX and CUR could induce the immunogenic cell death(ICD)to promote adaptive anti-tumor immunogenicity and inhibit immunosuppression through suppressing the activity of indoleamine 2,3-dioxygenase 1(IDO1)enzyme respectively.Therefore,the synergism of this intelligent nanomedicine can suppress primary breast tumor growth and inhibit their lung metastasis.

关 键 词：Controllable upper critical solution temperature(UCST) Immunogenic cell death(ICD) Indoleamine 2 3-dioxygenase 1(IDO1) Drug delivery Cancer chemoimmunotherapy 

分 类 号：R318[医药卫生—生物医学工程] R392[医药卫生—基础医学]