An Integrated Nanoaircraft Carrier Modulating Antitumor Immunity to Enhance Immune Checkpoint Blockade Therapy. (27th August 2021)

• Record Type: Journal Article
• Authors: Liang, Shuang; Liu, Yang; Gao, Tong; Liu, Xiaoqing; Zhang, Zipeng; Mu, Weiwei; Fu, Shunli; Liu, Meichen; Liu, Yongjun; Zhang, Na
• Is Part Of: Advanced functional materials. Volume 31:Number 48(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-27
• Subjects: immune checkpoint blockade therapy -- immunosuppression -- nanoaircraft carriers -- reducing tumor burden -- T‐cell intratumoral infiltration; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202106123
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Immune checkpoint blockade (ICB) therapy revolutionizes cancer therapeutics. However, the effectiveness of ICB therapy is restricted. Focusing on the tumor itself and the immune system, an integrated nanoaircraft carrier that coloaded three therapeutic agents (NNG/OTC) to eradicate tumor cells, enhance T‐cells intratumoral infiltration, and relieve the inhibition of tumor immunosuppressive microenvironment (TIM) is designed. First, tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) is used to combine with oxaliplatin for reducing tumor burden. Second, oxaliplatin is used to elicit immunogenic cell death and combine with cytosine‐phosphate‐guanine (CpG) to promote dendritic cells maturation, ultimately increasing T‐cells intratumoral infiltration. Third, CpG is further used to repolarize M2 type of tumor‐associated macrophages, thus reversing immunosuppression of TIM. The nanoaircraft carrier can effectively arrive at the tumor site and detach small‐sized nanoparticles under a high concentration of matrix metalloproteinase‐2, which promotes deep tumor penetration. Under the mediation of targeting ligands, three therapeutic agents loaded in small‐sized nanoparticles could be launched to their target cells. NNG/OTC modulates the antitumor immunity and exhibits excellent tumor inhibition when in combination with ICB therapy, indicating the increased response of ICB therapy. Collectively, NNG/OTC can co‐deliver various drugs with different physicochemical properties and provide a promising strategy for enhancing ICB therapy. Abstract : A novel integrated nanoaircraft carrier that can co‐deliver various therapeutic agents with different physicochemical properties is obtained, which can simultaneously target tumor cells and the immune system. The integrated nanoaircraft carrier eradicates tumor cells, enhances T‐cells intratumoral infiltration, and regulates the inhibition of tumor immunosuppressive microenvironment to T‐cells, thus enhancing immune checkpoint blockade therapy.