Journal Article

Selective enhanced cytotoxicity of amino acid deprivation for cancer therapy using thermozyme functionalized nanocatalyst

Huo, Rui, Huang, Mingwang, Xie, Guiqiu, Gao, Renjun, Zhang, Lijuan, Wang, Fang, Tang, Xiuhui

2024

Overview

Background Enzyme therapy based on differential metabolism of cancer cells has demonstrated promising potential as a treatment strategy. Nevertheless, the therapeutic benefit of reported enzyme drugs is compromised by their uncontrollable activity and weak stability. Additionally, thermozymes with high thermal-stability suffer from low catalytic activity at body temperature, preventing them from functioning independently. Results Herein, we have developed a novel thermo-enzymatic regulation strategy for near-infrared (NIR)-triggered precise-catalyzed photothermal treatment of breast cancer. Our strategy enables efficient loading and delivery of thermozymes (newly screened therapeutic enzymes from thermophilic bacteria) via hyaluronic acid (HA)-coupled gold nanorods (GNRs). These nanocatalysts exhibit enhanced cellular endocytosis and rapid enzyme activity enhancement, while also providing biosafety with minimized toxic effects on untargeted sites due to temperature-isolated thermozyme activity. Locally-focused NIR lasers ensure effective activation of thermozymes to promote on-demand amino acid deprivation and photothermal therapy (PTT) of superficial tumors, triggering apoptosis, G1 phase cell cycle arrest, inhibiting migration and invasion, and potentiating photothermal sensitivity of malignancies. Conclusions This work establishes a precise, remotely controlled, non-invasive, efficient, and biosafe nanoplatform for accurate enzyme therapy, providing a rationale for promising personalized therapeutic strategies and offering new prospects for high-precision development of enzyme drugs. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Advanced local therapies from nano-engineered implants and biomaterials / Amino acid deprivation / Amino acids / Apoptosis / Bacteria / Bioavailability / Biotechnology / Body temperature / Breast cancer / Cancer / Cancer therapies / Care and treatment / Catalysis / Catalytic activity / Cell cycle / Cell growth / Cell migration / Chemistry / Chemistry and Materials Science / Cytotoxicity / Deprivation / Drug development / Drugs / Endocytosis / Enzymatic activity / Enzyme activity / Enzymes / Fourier transforms / G1 phase / Health aspects / Hyaluronic acid / Lasers / Malignancy / Molecular Medicine / Nanorods / Nanotechnology / Near infrared radiation / Precise endocytosis / Remote control / Remote regulation / Stability / Therapy / Thermocatalysis-photothermal therapy / Thermophilic bacteria / Thermozyme drug / Tumors