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<p>SO<sub>2</sub> gas-therapy provides sustained assistance for augmenting the efficacy of ROS-based modalities due to its powerful tumor microenvironment-reversing capabilities. However, the inefficient delivery and insufficient generation of SO<sub>2</sub> have greatly limited the efficacy of SO<sub>2</sub> therapy. Herein, we designed a programmed-responsive SO<sub>2</sub>/nanozyme synergistic therapeutic nanomedicine based on the polypeptide-type copolymer of poly(ethylene glycol)-<i>b</i>-poly(L-lysine) (PEG-<i>b</i>-PLL). By taking advantage of the abundant amine groups on the PLL blocks, a dual-locked SO<sub>2</sub> releasing system was fabricated by grafting SO<sub>2</sub> prodrug onto the PLL blocks through GSH-responsive covalent bonds and crosslinking the remaining amine groups with disulfide-connectors to form an outer stimulation-responsive shell. Such a dual encapsulation effectively prevented the premature release of SO<sub>2</sub> in normal cells and guaranteed its timely and sustained release, making the SO<sub>2</sub> therapeutic processes finely coordinate with the catalytic processes of nanozymes loaded in the micellar core. The well-matching of SO<sub>2</sub> and nanozyme resulted in the efficaciously remodeling of the tumor redox microenvironment, thus significantly enhancing the overall efficacy of chemodynamic therapy (CDT). This optimized multimodal cooperation strategy provides delicate control for improving the synergistic therapeutic efficiencies, which is anticipated to advance the ROS-based cancer treatments.</p>

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Dual-locked SO2/nanozyme delivery nanoplatform for programmed synergistic gas/chemodynamic anticancer therapy

  • 期刊论文

  • 发表日期：

    2025年6月30日

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  • Tianyu Zhong,
  • Tao Zhu,
  • Ya Li,
  • Shuqi Wang,
  • Quan Jiang,
  • Yong Zhang,
  • Yongsheng Li,
  • Yuanyuan Cao

摘要

SO2 gas-therapy provides sustained assistance for augmenting the efficacy of ROS-based modalities due to its powerful tumor microenvironment-reversing capabilities. However, the inefficient delivery and insufficient generation of SO2 have greatly limited the efficacy of SO2 therapy. Herein, we designed a programmed-responsive SO2/nanozyme synergistic therapeutic nanomedicine based on the polypeptide-type copolymer of poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL). By taking advantage of the abundant amine groups on the PLL blocks, a dual-locked SO2 releasing system was fabricated by grafting SO2 prodrug onto the PLL blocks through GSH-responsive covalent bonds and crosslinking the remaining amine groups with disulfide-connectors to form an outer stimulation-responsive shell. Such a dual encapsulation effectively prevented the premature release of SO2 in normal cells and guaranteed its timely and sustained release, making the SO2 therapeutic processes finely coordinate with the catalytic processes of nanozymes loaded in the micellar core. The well-matching of SO2 and nanozyme resulted in the efficaciously remodeling of the tumor redox microenvironment, thus significantly enhancing the overall efficacy of chemodynamic therapy (CDT). This optimized multimodal cooperation strategy provides delicate control for improving the synergistic therapeutic efficiencies, which is anticipated to advance the ROS-based cancer treatments.