Bimetallic Ions Functionalized Metal–Organic‐Framework Nanozyme for Tumor Microenvironment Regulating and Enhanced Photodynamic Therapy for Hypoxic Tumor

Abstract

Photodynamic therapy (PDT), as a light irradiation inducing reactive oxygen species (ROS) generation for cancer treatment, offers facile and promising solutions with respect to spatiotemporal control of ROS generation, and minimizes the systemic toxicity and side effects for highly precise tumor therapy. However, the PDT efficiency is often severely compromised by the complex tumor microenvironment (TME), such as the hypoxic condition and overexpressed antioxidants. Here, for the first time, a bimetallic ion–modified metal−organic framework nanozyme (Zr4+‐MOF‐Ru3+/Pt4+‐Ce6@HA, ZMRPC@HA) is designed. ZMRPC@HA with catalase (CAT) and glutathione oxidase (GSHOx) mimetic activities, can efficiently regulate TME by generation of O2 and deplete the GSH synergistically for enhancing the long‐term PDT efficacy toward the hypoxic tumor. The in vitro cell inhibition and in vivo on tumor xenograft evaluations demonstrate the PDT strategy by using ZMRPC@HA can successfully inhibit the differentiation and proliferation of tumor cells under a 660 nm laser irradiation in deep tissues. These findings open a new avenue for the design of multimetallic ions functionalized MOF‐based nanozymes with multienzyme mimetic activities toward the antitumor and various other biological applications.

Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment

“…PDT involves the utilization of photosensitizer-converted light energy to generate cytotoxic 1 O 2 upon exposure to light irradiation. − However, the efficacy of PDT alone is often compromised by the hypoxic tumor environment. Consequently, nanozymes with CAT-like activity offer a solution to this predicament by converting high concentrations of H 2 O 2 in the tumor area into O 2 , thereby reinforcing PDT. , For example, Liu et al developed a precisely defined and homogeneous nanoplatform (Ce6/Ftn@MnO 2 ) comprising MnO 2 as a CAT-like nanozyme, chlorin e6 (Ce6) as a photosensitizer, and ferritin (Ftn) as an inherent tumor-targeting nanovector for enhanced PDT of tumors (Figure A) . The in vitro experiment demonstrated that groups II (Ce6/Ftn@MnO 2 + H 2 O 2 , pH 7.4) and III (Ce6/Ftn@MnO 2 + H 2 O 2 , pH 6.0) exhibited a higher concentration of dissolved O 2 compared to group I (H 2 O 2 ), thereby confirming superior CAT-like performance of the Ce6/Ftn@MnO 2 (Figure B).…”

Single-Atom-Based Nanoenzyme in Tissue Repair

“…This involves analyzing interactions at the molecular level using techniques such as Raman spectroscopy to detect changes in cell membrane composition and structure. Concurrently, conducting relevant in vivo and in vitro experiments is critical for assessing toxicity and biocompatibility. − To this end, ongoing research into the complex mechanisms of SAzymes toxicity is necessary to ensure their responsible utilization in biomedical fields.…”

Engineered Extracellular Vesicles to Enhance Antigen Presentation for Boosting Light‐Driven Tumor Immunotherapy

“…Many kinds of inorganic nanomaterials can be intracellularly synthesized through bioreduction, detoxification, or biomineralization. [21] Because of their unique physicochemical properties, they have shown distinguished performance in different types of cancer treatment including but not limited to photothermal therapy (PTT), [22,23] chemodynamic therapy (CDT), [24,25] enhanced radiotherapy (RT), [26,27] etc. Usually, such therapeutic modalities can elicit immunogenic cell death (ICD) via inducing dying tumor cells to release damage-associated molecular patterns (DAMPs), which have potential to promote dendritic cells (DCs) maturation for enhanced antitumor immunity.…”