Rationally designed anti-autophagy nanosystems for reversing the immunosuppressive network in the tumor environment
Year: 2025
Type: article
Abstract: AIMS: To develop a nano-immunotherapy system combining autophagy inhibition and innate immune activation to reverse the immunosuppressive tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). MATERIALS & METHODS: The pH-responsive polymer PC7A was utilized to co-deliver the autophagy inhibitor chloroquine (CQ) and the STING agonist cyclic diguanylate (CDG), forming the CQCP nanosystem. In vitro and in vivo experiments evaluated autophagy inhibition, MHC-I expression, dendritic cell activation, tumor infiltration of lymphocytes, and survival in PDAC-bearing mice. RESULTS: < 0.001), and systemic immune activation in peripheral lymphoid tissues was observed. CQCP achieved an 86% survival rate in tumor-bearing mice, significantly outperforming monotherapies or free drug combinations. CONCLUSIONS: The CQCP system synergistically reverses PDAC immunosuppression by restoring antigen presentation and activating innate immunity. This dual-targeted strategy demonstrates robust antitumor efficacy and offers a promising immunotherapy approach for PDAC.
Source: Nanomedicine
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
Funder: Tsinghua University
OpenAlex ID: W4410604151