Light-activatable liposomes for repetitive on-demand drug release and immunopotentiation in hypoxic tumor therapy.

Abstract

External stimuli-responsive nanomedicine with desirable repetitive on-demand drug release character is postulated to greatly accommodate patients' flexible medication regime. To this object, light-activatable liposomes (Pt/Ce6-LP) integrated with both a Ce6 photodynamic component and a tetravalent platinum prodrug (Pt(IV)) chemotherapeutic component are engineered. This multifunctional system was rationally designed using unsaturated phospholipid to achieve repetitive on-demand drug release under discontinuous light irradiation, thus performing chemo-photodynamic therapy effect and immunopotentiation in hypoxic tumor. Furthermore, glutathione (GSH) consumption during transformation from Pt(IV) prodrug to Pt(II) can avoid depletion of reactive oxygen species (ROS) in photodynamic therapy (PDT). Note this positive feedback loop appears to remodel the redox balance of H2O2 and GSH in tumors, alleviating the hypoxic tumor microenvironment. The alleviated hypoxia is found to be critical to the enhancement of PDT efficacy, reversal of cisplatin resistance in tumors, and polarization of tumor-associated macrophages (TAMs) to the immunocompetent M1-phynotype. Pt/Ce6-LP with light radiation demonstrates significant antitumor effect and persistent post-medication inhibition in patient-derived tumor xenograft model of hepatocellular carcinoma.

• Authors: Yuanyuan Yang, Xin Liu, Wen Ma, Qing Xu, Gui Chen, Yufei Wang, Haihua Xiao, Nan Li, Xing-Jie Liang, Meng Yu, Zhiqiang Yu
• Journal: Biomaterials (Biomaterials) Vol. 265 Pg. 120456 (01 2021) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 33099066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Liposomes
• Photosensitizing Agents
• Hydrogen Peroxide

Topics

• Cell Line, Tumor
• Drug Liberation
• Humans
• Hydrogen Peroxide
• Hypoxia (drug therapy)
• Liposomes
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)