Wu Tong, Song Huijuan, Wang Rijie, Wang Weiwei, Xing Jinfeng
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, PR China.
Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300350, PR China.
Int J Biol Macromol. 2025 Mar;293:139363. doi: 10.1016/j.ijbiomac.2024.139363. Epub 2024 Dec 30.
Exosomes as a unique drug delivery system provide a new choice for tumor therapy. However, the in vitro functionalization of exosomes and the process of circulating drug delivery can easily cause exosome degradation and drug loss, thus reducing the efficiency of drug delivery. In this work, based on the endocyto-fusion-exocytosis pathway of exosome formation, a multifunctional hyaluronic acid nanogel loaded with the antiangiogenic drug vatalanib and the near-infrared photothermal agent indocyanine green (ICG) was designed. Lysosome escape and photothermal therapy were combined to promote exosome production. Hyaluronic acid nanogels were endocytosed by tumor cells with CD44 mediation, forming intracellular vesicle-coated nanogels, which were subsequently degraded by hyaluronidase with high expression in tumor cells. Anti-angiogenic signals in intracellular vesicles were then delivered to vascular endothelial cells by exosomes through membrane fusion and exocytosis, which inhibited tumor angiogenesis to prevent tumor proliferation and metastasis. Cell experiments and tumor models demonstrate that our therapeutic strategy can achieve effective tumor inhibition.
外泌体作为一种独特的药物递送系统，为肿瘤治疗提供了新的选择。然而，外泌体的体外功能化以及循环药物递送过程容易导致外泌体降解和药物损失，从而降低药物递送效率。在这项工作中，基于外泌体形成的内吞-融合-胞吐途径，设计了一种负载抗血管生成药物瓦他拉尼和近红外光热剂吲哚菁绿（ICG）的多功能透明质酸纳米凝胶。将溶酶体逃逸和光热疗法相结合以促进外泌体产生。透明质酸纳米凝胶在CD44介导下被肿瘤细胞内吞，形成细胞内囊泡包裹的纳米凝胶，随后被肿瘤细胞中高表达的透明质酸酶降解。然后，细胞内囊泡中的抗血管生成信号通过外泌体通过膜融合和胞吐作用传递给血管内皮细胞，从而抑制肿瘤血管生成，防止肿瘤增殖和转移。细胞实验和肿瘤模型表明，我们的治疗策略可以实现有效的肿瘤抑制。
