Self-Supply Oxygen ROS Reactor via Fenton-like Reaction and Modulating Glutathione for Amplified Cancer Therapy Effect

Huanli Zhang; Wei Ma; Zhiqiang Wang; Xiaodan Wu; Hui Zhang; Wen Fang; Rui Yan; Yingxue Jin

doi:10.3390/nano12142509

Self-Supply Oxygen ROS Reactor via Fenton-like Reaction and Modulating Glutathione for Amplified Cancer Therapy Effect

Nanomaterials (Basel). 2022 Jul 21;12(14):2509. doi: 10.3390/nano12142509.

Authors

Huanli Zhang¹, Wei Ma¹, Zhiqiang Wang¹, Xiaodan Wu¹, Hui Zhang¹, Wen Fang¹, Rui Yan¹, Yingxue Jin¹

Affiliation

¹ Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China.

Abstract

Reactive oxygen species (ROS) are highly reactive oxidant molecules that can kill cancer cells through irreversible damage to biomacromolecules. ROS-mediated cancer therapies, such as chemodynamic (CDT) and photodynamic therapy (PDT), are often limited by the hypoxia tumor microenvironment (TME) with high glutathione (GSH) level. This paper reported the preparation, characterization, in vitro and in vivo antitumor bioactivity of a meso-tetra(4-carboxyphenyl)porphine (TCPP)-based therapeutic nanoplatform (CMMFTP) to overcome the limitations of TME. Using Cu²⁺ as the central ion and TCPP as the ligand, the 2D metal-organic framework Cu-TCPP was synthesized by the solvothermal method, then CMMFTP was prepared by modifying MnO₂, folic acid (FA), triphenylphosphine (TPP), and poly (allylamine hydrochloride) (PAH) on the surface of Cu-TCPP MOFs. CMMFTP was designed as a self-oxygenating ROS nanoreactor based on the PDT process of TCPP MOFs and the CDT process by Cu(II) and MnO₂ components (mainly through Fenton-like reaction). The in vitro assay suggested CMMFTP caused a 96% lethality rate against Hela cells (MTT analysis) in specific response to TME stimulation. Moreover, the Cu(II) and MnO₂ in CMMFTP efficiently depleted the glutathione (80%) in tumor cells and consequently amplified ROS levels to improve CDT/PDT effects. The FA-induced tumor targeting and TPP-induced mitochondria targeting further enhanced the antitumor activity. Therefore, the nanoreactor based on dual targeting and self-oxygenation-enhanced ROS mechanism provided a new strategy for cancer therapy.

Keywords: Fenton-like reaction; reactive oxygen species (ROS); self-supply oxygen; synergetic effect; tumor microenvironment (TME).

Grants and funding

This research was funded by the Joint Foundation of Natural Science Foundation Heilongjiang Province of China (LH2019H067), Young Academic Backbone of Harbin Normal University, China (12XQXG12) and the College Students Innovation and Entrepreneurship Training Program of Heilongjiang Province (202110231078). And the APC was funded by the Graduate Innovation Projects of Harbin Normal University (HSDSSCX2021–112).