Yijun Wu, Xiaochen Wang, Longxia Li, Mingyang Wang, Sui Tian, Jinfeng Song, Yunfeng Ma
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Preparation of Glutathione-Regulated Sorafenib Targeted Nanodrug Delivery System and Its Antihepatocellular Carcinoma Activity
To enhance the therapeutic effect of sorafenib (SOR) on liver cancer, we have developed a targeted nanodrug delivery system with glutathione (GSH) downregulation functionality. The preparation process comprises the synthesis of amino-functionalized mesoporous silica nanoparticles (MSN-NH2), surface modification with ethacrynic acid (EA), loading of SOR into the pores, and final surface coating with hyaluronic acid (HA) to obtain SOR@MSN-EA@HA (SMEH) nanoparticles. SMEH nanoparticles specifically enter tumor cells via CD44 receptor-mediated endocytosis. EA binds to GSH to consume it, while SOR is slowly released from the pores to exert antitumor effects while inhibiting GSH production. This results in sustained oxidative stress in the cells, thus enhancing the antitumor efficacy. Both in vitro and in vivo antitumor experiments as well as hemolysis tests have demonstrated that SMEH nanoparticles can accurately target liver cancer cells, effectively downregulate GSH concentration, exhibit good antitumor effects, and possess excellent safety, showing great potential in tumor treatment.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
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Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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