| Autor: |
TianCheng Wang, MinZhao Lin, JunJie Mao, LiRong Tian, HaiRun Gan, XinYan Hu, LeYe Yan, HaoYu Long, JianXun Cai, XiaoDi Zheng, YuDong Xiao, Dan Li, XinTao Shuai, PengFei Pang |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
ACS applied materialsinterfaces. |
| ISSN: |
1944-8252 |
| Popis: |
Immune checkpoint blockade (ICB) utilizing programmed death ligand-1 (PD-L1) antibody is a promising treatment strategy in solid tumors. However, in fact, more than half of hepatocellular carcinoma (HCC) patients are unresponsive to PD-L1-based ICB treatment due to multiple immune evasion mechanisms such as the hyperactivation of inflammation pathway, excessive tumor-associated macrophages (TAMs) infiltration, and insufficient infiltration of T cells. Herein, an inflammation-regulated nanodrug was designed to codeliver NF-κB inhibitor curcumin and PD-L1 antibody to reprogram the tumor microenvironment (TME) and activate antitumor immunity. The nanodrug accumulated in TME by an enhanced permeability and retention effect, where it left antibody to block PD-L1 on the membrane of tumor cells and TAMs due to pH-responsiveness. Simultaneously, a new curcumin-encapsulated nanodrug was generated, which was easily absorbed by either tumor cells or TAMs to inhibit the nuclear factor kappa-B (NF-κB) signal and related immunosuppressive genes. The inflammation-regulated nanodrug possessed good biocompatibility. Simultaneously, it reprogrammed TME effectively and exhibited an effective anticancer effect in immunocompetent mice. Overall, this study provided a potent strategy to improve the efficiency of ICB-based treatment for HCC. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
