Tumor-Activated Carrier-Free Dual-Prodrug Nanoassemblies for Synergistic Chemo-Immunotherapy

Authors:
Publisher website
Google Scholar
Abstract
Chemo-immunotherapy is limited by the poor bioavailability, nonspecific distribution, and systemic toxicity of free drugs. Here, we develop a reactive oxygen species (ROS)-responsive prodrug strategy by conjugating paclitaxel (PTX) and the TLR7/8 agonist resiquimod (R848) with a phenylboronic ester (PBE) moiety to generate two ROS-activatable prodrugs, PTX–PBE and R848–PBE. These prodrugs spontaneously coassemble into carrier-free nanoparticles (PR NPs) with ultrahigh loading efficiency and tunable drug ratios. PBE modification improves systemic stability while enabling ROS-triggered drug release in the tumor microenvironment, allowing PTX-mediated immunogenic cell death and R848-mediated innate immune activation. In colorectal cancer models, PR NPs suppress tumor growth, reduce systemic toxicity, and remodel the tumor immune microenvironment by promoting antitumor immune responses. This prodrug engineering strategy provides a high-loading, activatable, and carrier-free platform for chemo-immunotherapy with potential for cancer treatment.
Funding Information
  • Health Commission of Jilin Province (2025SCZ59)
  • Ministry of Science and Technology of the People's Republic of China (2025YFE0114200)
  • Jilin University (2022JBGS04)
  • Jilin University (2025-CJUH-XTCX2.0-008)
  • Jilin University (2026B24)
  • Jilin University (CJUH-SINH009)
  • Jilin University (Collaborative Innovation Project (Version 1.0) of)
  • Department of Science and Technology of Jilin Province (20240501002GH)
  • Department of Science and Technology of Jilin Province (20260101020JJ)
  • Department of Science and Technology of Jilin Province (CBS2026005)
  • Department of Science and Technology of Jilin Province (YDZJ202102CXJD020)
  • Department of Science and Technology of Jilin Province (YDZJ202602CXJD007)
  • Jilin Province Development and Reform Commission (2021C023)
  • Education Department of Jilin Province (JJKH20250194BS)
  • National Natural Science Foundation of China (NSFC) (32401174)
  • National Natural Science Foundation of China (NSFC) (32571686)
  • National Natural Science Foundation of China (NSFC) (82572298)
  • National Natural Science Foundation of China (NSFC) (U24A20477)
  • Science and Technology Department, Henan Province (2024001)

This publication has 42 references indexed in Scilit: