1. Academic Validation
  2. Functional exosomes modified with chitosan effectively alleviate anthracycline-induced cardiotoxicity

Functional exosomes modified with chitosan effectively alleviate anthracycline-induced cardiotoxicity

  • Int J Biol Macromol. 2024 Aug 5;277(Pt 3):134495. doi: 10.1016/j.ijbiomac.2024.134495.
Zhiwei Wen 1 Shuiling Qin 1 Huajie Huang 1 Xingle Xia 1 Wei Zhang 1 Wei Wu 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Guilin Medical University, Guilin 541199, China.
  • 2 School of Pharmacy, Guilin Medical University, Guilin 541199, China; Guangxi Key Laboratory of Drug Discovery and Optimization, School of Pharmacy, Guilin Medical University, Guilin 541199, China. Electronic address: wuwei@glmc.edu.cn.
Abstract

Anthracyclines belong to a class of anti-tumor Antibiotics, and their severe cardiotoxicity significantly limits their clinical use. Exosomes play key roles in intercellular communication, characterized by high biocompatibility and specific tissue and organ homing effects. In this study, doxorubicin, an anthracycline Anticancer drug widely used in clinical chemotherapy, was selected as a model drug. To address the significant cardiotoxicity associated with doxorubicin, tumor exosomes are utilized as drug carriers. The homing effect of autologous exosomes enhances drug uptake by tumor cells and reduces cardiotoxicity. To enhance the stability of exosomes, improve therapeutic effectiveness, and reduce toxic side effects, chitosan was utilized to modify the surface of exosomes. Chitosan has a specific anti-tumor effect because it can target the CD44 receptor of tumor stem cells and interact with tumor cells through charge adsorption. Through in vitro cell experiments, in vivo pharmacokinetic experiments, and an in situ ectopic nude mouse tumor model, the study demonstrated that chitosan-modified tumor exosomes significantly alleviated the severe cardiotoxicity of doxorubicin, while also showing remarkable anti-tumor efficacy. This study introduces a novel approach to reduce the adverse side effects of anthracycline chemotherapeutic drugs and presents a highly promising nanocarrier delivery system.

Keywords

Antitumor; Chitosan; Doxorubicin; Drug delivery; Exosomes.

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