Biomimetic Platinum Nanozyme Immobilized on 2D Metal–Organic Frameworks for Mitochondrion-Targeting and Oxygen Self-Supply Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) as a noninvasive therapy mode has attracted considerable attention in the field of oncotherapy. However, the PDT efficacy is restricted either by the tumor hypoxia environment or the inherent properties of photosensitizers (PSs) including bad water solution, photobleaching, and easy aggregation. Herein, we designed and synthesized a new two-dimensional (2D) metal−organic framework, Sm-tetrakis(4-carboxyphenyl)porphyrin (TCPP) nanosheets, by assembling transition metal ions (Sm 3+ ) and PSs (TCPP), on which the catalase (CAT)-mimicking platinum nanozymes were then in situ grown for sufficient oxygen supply during PDT. The prepared Sm-TCPP with nanoplate morphology (∼100 nm in diameter) and ultrathin thickness (<10 nm) showed significantly enhanced 1 O 2 generation capacity due to the improved physicochemical properties and the enhanced intersystem crossing from heavy Sm nodes. More importantly, the CAT-mimicking Pt nanozyme on the Sm-TCPP nanosheets could effectively convert over-expressed H 2 O 2 in the tumor microenvironment into O 2 to relieve tumor hypoxia. Further, the triphenylphosphine (TPP) molecule was introduced to Sm-TCPP-Pt to develop a mitochondrion-targeting and O 2 self-supply PDT system. The in vitro and in vivo experimental results based on the MCF-7 breast cancer model revealed that Sm-TCPP-Pt/TPP could relieve tumor hypoxia and the generated reactive oxygen species nearby intracellular mitochondria significantly induced cell apoptosis. This study offers an engineering strategy to integrate 2D PS-based metal−organic frameworks and nanozymes into a nanoplatform to surmount the pitfalls of traditional PDT.

Pd‐Single‐Atom Coordinated Biocatalysts for Chem‐/Sono‐/Photo‐Trimodal Tumor Therapies

“…They utilize the sono-irradiation or photoexcitation to generate highly reactive oxygen species (ROS), such as singlet oxygen ( 1 O 2 ) and hydroxyl radicals (•OH). [13][14][15][16][17] Owing to the temporal and spatial management over the localization of the sound or light, the ROS can be generated precisely in the tumor tissues instead of normal tissue, thus minimizing the side effects. [18][19][20] The unique quantity of deep tissue penetration and little side The diversity, complexity, and heterogeneity of malignant tumor seriously undermine the efficiency of mono-modal treatment.…”

Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy

“…Chitosan-CyI (CC) nanoparticles were first formed via reactions between carboxyl groups of CyI with amino groups of chitosan. MCC nanosystems were then obtained through a biomineralization procedure 19 , which induced the formation of metal ions into metal oxide nanoclusters under room temperature. The solution color changed from green to brown during the formation of MCC (Figure 1 B).…”

“…In recent years, various O 2 -evolving agents, such as HbO 2 , catalase, and perfluorocarbon, have been incorporated into PDT nanosystems 12 - 19 . Although these nanosystems have shown potentials for self-supplying oxygen in PDT processes, they still cannot counterbalance the GSH-induced depletion of singlet oxygen.…”

Recent Advances in Photodynamic Therapy for Deep-Seated Tumors with the Aid of Nanomedicine

“…Some strategies using nanomaterials with CAT-like catalysis activity were developed and revealed excellent performance in the decomposition of hydrogen peroxide and oxygen generation in cancer cells [ 76 , 77 , 78 ]. A 2D MOF nanosheet assembled by transition metal ions (Sm 3+ ), platinum, and TCPP presented catalase-like activity for sufficient oxygen supply during PDT [ 79 ]. V 2 O 5 nanoparticles exhibited their potential to regulate the oxygen amount in the TME through their intrinsic peroxidase-like activity to decompose H 2 O 2 to O 2 [ 80 ].…”