Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor.

Abstract

Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.

• Authors: Haoyu Guo, Lutong Wang, Wei Wu, Mingke Guo, Lingkai Yang, Zhenhao Zhang, Li Cao, Feifei Pu, Xin Huang, Zengwu Shao
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 351 Pg. 151-163 (11 2022) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 36122895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Tirapazamine
• Indocyanine Green
• Photosensitizing Agents

Topics

• Humans
• Reactive Oxygen Species (metabolism)
• Biomimetics
• Tirapazamine
• Photochemotherapy
• Neoplasms (drug therapy, pathology)
• Indocyanine Green (therapeutic use)
• Hypoxia
• Nanoparticles
• Nanotechnology
• Cell Line, Tumor
• Photosensitizing Agents
• Tumor Microenvironment