2. Academic Validation
  3. Electrically activated polymetallic nanocrystals for long-term tumor suppression via oxygen-independent ROS generation and electro-immunotherapy

Electrically activated polymetallic nanocrystals for long-term tumor suppression via oxygen-independent ROS generation and electro-immunotherapy

  • J Control Release. 2024 May 15:370:677-690. doi: 10.1016/j.jconrel.2024.05.017.
Manchun Wang 1,  Gui Chen 2,  Ben Hu 1,  Fengling Zhang 1,  Qinqin Xu 1,  Lei Li 3,  Qiye Xi 1,  Jun Liu 4,  Zhiqiang Yu 5,  Peng Cao 6,  Yongxia Wang 7,  Meng Yu 8
Affiliations

Affiliations

  • 1 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 2 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan 523018, China.
  • 3 Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
  • 4 Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang 110000, China.
  • 5 Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan 523018, China.
  • 6 Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang 110000, China. Electronic address: Pengcao518@163.com.
  • 7 Breast Department, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan 523018, China. Electronic address: wyx0148@163.com.
  • 8 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address: yumeng999@smu.edu.cn.
PMID: 38740093 DOI: 10.1016/j.jconrel.2024.05.017
Abstract

The low oxidation level and immunosuppressive microenvironment within hypoxic tumor tissue are critical factors contributing to the inefficacy of various anti-tumor strategies. Herein, we have designed a novel intravenous injection nanoplatform to conduct electro-immunotherapy, based on phospholipid-modified PtPd nanocrystals loaded with the immunoregulator IPI549 (LP@Pt-Pd@IPI549 nanoparticles, LPPI). LPPI responds to Reactive Oxygen Species (ROS), triggering a cascade of therapeutic effects that overcome hypoxia-related resistance and effectively eradicate hypoxic tumors. Firstly, under electric field exposure, LPPI relied on water rather than oxygen to generate abundant ROS under hypoxic conditions for tumor electrodynamic therapy (EDT). Moreover, the generated ROS further induced the disintegration of the outer phospholipid membrane of LPPI, leading to the release of the immunoregulator and inhibition of myeloid-derived suppressor cells (MDSCs), triggering cascade immune responses. Additionally, the immunomodulatory effects of IPI549, in synergy with the immunogenic cell death (ICD) induced by EDT, reversed the immunosuppressive microenvironment contributing to tumor resistance. In summary, EDT transiently killed tumor cells while simultaneously generating antigen release, instigating an adaptive immune response for electro-immunotherapy, resulting in a potent and long-lasting tumor inhibition effect.

Keywords

Antitumor immunity; Electrical activation; Hypoxic tumor microenvironment; Oxygen-independent; Polymetallic nanocrystals.

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  • HY-100716
    99.68%, PI3Kγ Inhibitor