All-in-One Theranostic Nanoagent with Enhanced Reactive Oxygen Species Generation and Modulating Tumor Microenvironment Ability for Effective Tumor Eradication

TLDR

ROS‑mediated therapies such as PDT and CDT are limited by oxygen dependence, photosensitizer flaws, and stringent Fenton reaction conditions. CFNs generate O₂ and deplete GSH to alleviate tumor hypoxia and antioxidant defenses, enabling photo‑enhanced CDT and improved PDT. CFNs exhibit enhanced ROS generation under 650 nm laser via electron transfer and photo‑enhanced Fenton reaction, high photothermal conversion at 808 nm, and a relaxivity of 468.06 mM⁻¹ s⁻¹, confirming their efficacy as an all‑in‑one theranostic platform combining PDT, photo‑enhanced CDT, PTT, MRI, and tumor microenvironment modulation.

Abstract

Despite regulation of the reactive oxygen species (ROS) level is an intelligent strategy for cancer therapy, the therapeutic effects of ROS-mediated therapy (including photodynamic therapy (PDT) and chemodynamic therapy (CDT)) are limited by oxygen reliance, inherent flaws of traditional photosensitizers, and strict reaction conditions of effective Fenton reaction. Herein, we reported biocompatible copper ferrite nanospheres (CFNs) with enhanced ROS production under irradiation with a 650 nm laser through direct electron transfer and photoenhanced Fenton reaction and high photothermal conversion efficiency upon exposure to an 808 nm laser, exhibiting a considerable improved synergistic treatment effect. Importantly, by exploiting the properties of O2 generation and glutathione (GSH) depletion of CFNs, CFNs relieve the hypoxia and antioxidant capability of the tumor, achieving photoenhanced CDT and improved PDT. The high relaxivity of 468.06 mM–1 s–1 enables CFNs to act as an outstanding contrast agent for MRI in vitro and in vivo. These findings certify the potential of such "all in one" nanotheranostic agent integrated PDT, photoenhanced CDT, photothermal therapy (PTT), and MRI imaging capabilities along with modulating the tumor microenvironment function in theranostics of cancer.