Photothermal Nanozymatic Nanoparticles Induce Ferroptosis and Apoptosis through Tumor Microenvironment Manipulation for Cancer Therapy

Abstract

It is highly desirable to design a single modality that can simultaneously trigger apoptosis and ferroptosis to efficiently eliminate tumor progression. Herein, a nanosystem based on the intrinsic properties of tumor microenvironment (TME) is designed to achieve tumor control through the simultaneous induction of ferroptosis and apoptosis. CuCP molecules are encapsulated in a liposome‐based nanosystem to assemble into biocompatible and stable CuCP nanoparticles (CuCP Lipo NPs). This nanosystem intrinsically possesses nanozymatic activity and photothermal characteristics due to the property of Cu atoms and the structure of CuCP Lipo NPs. It is demonstrated that the synergistic strategy increases the intracellular lipid‐reactive oxides species, induces the occurrence of ferroptosis and apoptosis, and completely eradicates the tumors in vivo. Proteomics analysis further discloses the key involved proteins (including Tp53, HMOX1, Ptgs2, Tfrc, Slc11a2, Mgst2, Sod1, and several GST family members) and pathways (including apoptosis, ferroptosis, and ROS synthesis). Conclusively, this work develops a strategy based on one nanosystem to synergistically induce ferroptosis and apoptosis in vivo for tumor suppression, which holds great potential in the clinical translation for tumor therapy.

Nanozyme-Based Remodeling of Disease Microenvironments for Disease Prevention and Treatment: A Review

“…In addition, due to the excellent photothermal effect of Bi 2 Te 3 nanosheets, the local heat generated by NIR-II light irradiation at 1064 nm not only directly ablates tumor cells but also enhances Au–Pd-catalytic-mediated tumor therapy. Yuan et al designed a nanosystem based on the intrinsic properties of TME to achieve tumor control by simultaneously inducing iron sagging and apoptosis. The nanosystem with intrinsic nanozyme activity and photothermal properties synergistically increased the intracellular lipid-active oxide species, induced the onset of iron sagging and apoptosis, and completely eradicated the tumor in vivo (Figure ).…”

“…Photothermal therapy induces tumor iron death and apoptosis. Reprinted with permission from ref . Copyright 2022 Wiley-VCH GmbH.…”

The applications of nanozymes in cancer therapy: based on regulating pyroptosis, ferroptosis and autophagy of tumor cells

“…This study showed that CuCP Lipo NP nanozymes synergistically induced ferroptosis and apoptosis in vivo to suppress tumor growth, showing great potential for clinical application in cancer therapy. 65…”

“…This study showed that CuCP Lipo NP nanozymes synergistically induced ferroptosis and apoptosis in vivo to suppress tumor growth, showing great potential for clinical application in cancer therapy. 65 In addition, Chang et al reported a novel strategy based on a single Pd atom nanozyme (Pd SAzyme) that enhanced the effectiveness of mild-temperature photothermal therapy (PTT) in cancer treatment by inducing ferroptosis. They constructed a nitrogen-coordinated carbon-supported Pd SAzyme by stripping a single atom from metal NPs.…”

Antitumor Effects of a Distinct Sonodynamic Nanosystem through Enhanced Induction of Immunogenic Cell Death and Ferroptosis with Modulation of Tumor Microenvironment

“…Thus, enhancing supplement of oxygen into tumor mass is a reasonable strategy to improve the therapeutic efficacy of SDT. Currently, various strategies have been designed to alleviate tumor hypoxia, such as introduction of microbubbles containing oxygen, in situ O 2 generation by metals, or catalase reacting with intratumoral H 2 O 2 and hemoglobin (Hb). − …”