Temperature‐Dependent CAT‐Like RGD‐BPNS@SMFN Nanoplatform for PTT‐PDT Self‐Synergetic Tumor Phototherapy

Abstract

Phototherapies such as photothermal therapy (PTT) and photodynamic therapy (PDT) are considered as alternatives for tumor remedies, because of their advantages of precise spatial orientation, minimally invasive, and nonradiative operation. However, most of phototherapeutic agents still suffer from low photothermal conversion efficacy and photodynamic performance, poor biocompatibility, and intratumor accumulation. Herein a biocompatible and target-deliverable PTT-PDT self-synergetic nanoplatform of RGD-BPNS@SMFN based on temperature-dependent catalase (CAT)-like behavior for tumor elimination is presented. The homogeneously dispersible nanoplatform is designed and fabricated through anchoring spherical manganese ferrite nanoparticles (SMFN) to black phosphorus nanosheets (BPNS), followed by arginine-glycine-aspartic acid (RGD) peptide modification. The nanoplatform exhibits excellent targeting ability and enhanced photonic response in comparison to plain BPNS and SMFN in vitro and in vivo. It is found that PTT and PDT have a self-synergetic behavior by means of the dual phototherapy mode interaction. The self-synergetic mechanism is mainly ascribed to PTT-promoted inherent CAT-like activity in the nanoplatform, which remodels the tumor hypoxia microenvironment and further ameliorates the PDT efficiency, providing promising high performance nanoplatform for synergetic dual mode phototherapy, enriching the design for the antitumor nanozyme.

Porous, Oxygen Vacancy Enhanced CeO2–x Microspheres with Efficient Enzyme-Mimetic and Photothermal Properties

“…A synergistic therapy agent with catalase-like activity can generate O 2 by decomposition of H 2 O 2 in a tumor microenvironment. 54,55,70,71 Higher oxygen concentration results in an enhancement in the generation rate of ROS that can be obtained from a photosensitizer immobilized on porous microspheres. 56−58 The photodynamic effect can be further enhanced by the generation of additional ROS (i.e., 1 dynamic action originated from either a photosensitizer or itself of therapy agent.…”

“…On the other hand, g-CeO 2– x microspheres have considerably higher photothermal performance and higher catalase-like activity with respect to plain CeO 2 microspheres. A synergistic therapy agent with catalase-like activity can generate O 2 by decomposition of H 2 O 2 in a tumor microenvironment. ,,, Higher oxygen concentration results in an enhancement in the generation rate of ROS that can be obtained from a photosensitizer immobilized on porous microspheres. − The photodynamic effect can be further enhanced by the generation of additional ROS (i.e., 1 O 2 •, and •O 2 – ) in the acidic tumor microenvironment due to the intrinsic oxidase- and peroxidase-like activities of g-CeO 2– x microspheres. The alleviation of hypoxia due to the catalase-like activity of synergistic therapy agent increases the efficiency of photodynamic action originated from either a photosensitizer or itself of therapy agent. − Hence, higher toxic effect leading to more efficient programmed death of tumor cells can be achieved by the simultaneous use of photodynamic action and catalase-like activity of g-CeO 2– x microspheres. − Consequently, the photothermal conversion ability accompanying with multifunctional enzyme-mimetic activity makes g-CeO 2– x microspheres a potential, promising synergistic therapy agent capable of overcoming hypoxia and generating additional toxic ROS in a tumor microenvironment which can be also exposed to photothermal action.…”

Progress and prospects of nanozymes for enhanced antitumor therapy

“…While PTT initiates tumor cell death predominantly through hyperthermia via plasmonic dissipation, which is converted by the energy of photons absorbed on the photothermal agent under near infrared (NIR) laser irradiation (Figure 3). However, strict conditions such as oxygen leakage, acidic condition and overexpression of GSH in the tumor microenvironment (TME) constrain the photothermal conversion efficacy and ROS production of Phototherapies (Song et al, 2022). Photosensitive nanozymes which can remodel the restricted environment in tumor are intensively studied by scientists to achieve better phototherapeutic efficiency (Wang et al, 2022a;Tang et al, 2022).…”

A two-pronged strategy to alleviate tumor hypoxia and potentiate photodynamic therapy by mild hyperthermia

“…30–33 Nonetheless, the catalase activity may not be optimal at body temperature and simply utilizing nanozymes to catalyze the endogenous H 2 O 2 for O 2 supply might not meet the rapid O 2 consumption of PDT. 34–39…”