“Butterfly-effect” nano-platforms for cascade immune amplification and tumor clearance through multi-modal therapy and immune sensitization

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2024-09, Vol.495, p.153103, Article 153103
• Main Authors: Chen, Haoyu, Kong, Xiaoying, Yan, Jiahui, Wang, Tianyi, Lv, Yaqian, Zhang, Fenglang, Liu, Danping, Qu, Yingshan, Fu, Jun, Han, Wei, Shi, Jinsheng
• Format: Article
• Language: English
• Subjects: Immunosuppressive reversal; Microwave dynamic therapy; Oxygen depletion; Photodynamic therapy; ROS amplification; Sonodynamic therapy
• ISSN: 1385-8947
• DOI: 10.1016/j.cej.2024.153103

•A natural nano-platform (melanin-hematoporphyrin-chloroquine R837-hyaluronic acid, MHRH) were prepared for ROS anti-tumor therapy in deep tumor tissues.•The natural MHRH nano-platform achieves potent ROS-based tumor dynamic therapy and significant immunosuppressive reversal with a simple intervention.•This work further proves the importance of immune activation in the treatment of PTT/PDT/SDT/WDT by means of thermal ablation and ROS, and provides a new clinical treatment paradigm for anti-tumor therapy. Combined dynamic tumor therapy of photodynamic therapy (PDT), sonodynamic therapy (SDT) and microwave dynamic therapy (MDT) can overcome the limitations of single reactive oxygen species (ROS)-based therapy (including limited tissue penetration depth and low ROS production). However, changes in the tumor microenvironment caused by ROS amplification and oxygen depletion induce severe immunosuppression at the tumor site, indicating effective immunosensitization of the tumors are urgently needed. Here, melanin-hematoporphyrin-chloroquine R837-hyaluronic acid (MHRH) nanoplatform that can simultaneously respond to 980 nm laser /1064 nm laser/ultrasonic/microwave was prepared for PDT/SDT/MDT, achieving outbreak of ROS in deep tumor. More importantly, the photothermal ablation and the participation of chloroquine R837 of MHRH NPs reversed the immunosuppression caused by oxygen depletion after ROS outbreak by promoting DCs maturation and secretion of macrophage exosomes. In summary, the natural MHRH nano-platform supplies an obvious anti-tumor “butterfly effect” through ROS outbreak, thermal ablation and significant immunosuppressive reversal, which provides a new and promising combined strategy of ROS-dynamic therapy and immune agonists in deep tumor tissues.