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

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.

A carbon dot-doped Cu-MOF-based smart nanoplatform for enhanced immune checkpoint blockade therapy and synergistic multimodal cancer therapy

“…Here we used RDPP to investigate the ability of Cu-MOF@RCD to produce oxygen in cells. 20 In the tests, anaerobic CT26 cells were pretreated with RDPP and Cu-MOF@RCD (0-90 min) and then irradiated by light (808 nm, 50 mW cm À2 ) for 10 min. Fig.…”

“…Therefore, CDT is expected to synergistically enhance PDT. 19,20 Photothermal therapy (PTT), which is based on local high temperature damage to tumor cells after irradiation, has attracted much attention in cancer treatment. 21,22 The photothermal effects can be amplified during the PDT and CDT, 23,24 because ROS produced by PDT and CDT inhibit the expression of heat shock proteins, thereby increasing cell heat sensitivity and enhancing the PTT effect.…”

Preparation of two‐dimensional porphyrin‐based MOFs/derivatives and their potential in sensing and biomedical applications

“… (A) The synthetic route and anti‐tumor mechanism of CMMFTP; (B) Photographs of tumor‐bearing mice in different experimental groups after 14 days of treatment; (C) images of tumors after different treatments. Reproduced with permission 74 . Copyright 2022, MDPI.…”

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

“…Cu + may, for instance, carry out Fenton-like reactions up to 160 times more quickly than Fe 2+ and is said to be more efective in producing toxic •OH in TME (pH 6.5-6.9) [121]. Tese Fenton-like reactions caused by transition metals have a number of benefts, including excellent performance in nearly neutral environments and a large natural abundance of structurally diverse oxide products [122].…”