Glucose-responsive enzymatic biomimetic nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic anticancer therapy.
Acta Biomater
; 172: 441-453, 2023 12.
Article
en En
| MEDLINE
| ID: mdl-37802309
ABSTRACT
Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H2O2 at the tumor site. More importantly, the self-supplied peroxide hydrogen (H2O2) can convert ABTS (2,2'-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe2+ arising from the reduction of Fe3+ by overexpressed GSH reacts with H2O2 to generate intensely reactive â¢OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies. STATEMENT OF SIGNIFICANCE:
Combinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H2O2. The self-supplied H2O2 initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous â¢OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nanopartículas
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Acta Biomater
Año:
2023
Tipo del documento:
Article
País de afiliación:
China