Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine

Bioactive Materials

Zhe Yang¹  Zhongmin Tian²  Yan Liu³  Xingcai Zhang³  Xiaoqing Guo⁴  Jinxuan Ma⁴  Li Zeng⁴  Di Gao⁴  Ying Wang⁴  Shuojia Chen⁴ 

[1] Corresponding author.;School of Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, United States;John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, United States;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;

关键词: Controllable upper critical solution temperature (UCST);    Immunogenic cell death (ICD);    Indoleamine 2,3-dioxygenase 1 (IDO1);    Drug delivery;    Cancer chemoimmunotherapy;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown