Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; Department of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China; Department of Pharmacy, Fudan University, Shanghai 201203, China.
Department of Pharmacy, Fudan University, Shanghai 201203, China.
Nanomedicine. 2018 Oct;14(7):1973-1985. doi: 10.1016/j.nano.2018.05.020. Epub 2018 Jun 20.
Exosomes have emerged as a promising drug carrier with low immunogenicity, high biocompatibility and delivery efficiency. Here in, we isolated exosomes from A33-positive LIM1215 cells (A33-Exo) and loaded them with doxorubicin (Dox). Furthermore, we coated surface-carboxyl superparamagnetic iron oxide nanoparticles (US) with A33 antibodies (A33Ab-US), expecting that these A33 antibodies on the surface of the nanoparticles could bind to A33-positive exosomes and form a complex (A33Ab-US-Exo/Dox) to target A33-positive colon cancer cells. The results showed that A33Ab-US-Exo/Dox had good binding affinity and antiproliferative effect in LIM1215 cells, as shown by increased uptake of the complex. In vivo study showed that A33Ab-US-Exo/Dox had an excellent tumor targeting ability, and was able to inhibit tumor growth and prolong the survival of the mice with reduced cardiotoxicity. In summary, exosomes functionalized by targeting ligands through coating with high-density antibodies may prove to be a novel delivery system for targeted drugs against human cancers.
外泌体作为一种有前途的药物载体，具有低免疫原性、高生物相容性和递药效率。在此，我们从 A33 阳性 LIM1215 细胞中分离出外泌体（A33-Exo）并将其装载多柔比星（Dox）。此外，我们将表面带羧基的超顺磁性氧化铁纳米粒子（US）用 A33 抗体（A33Ab-US）进行包被，期望这些纳米粒子表面的 A33 抗体能够与 A33 阳性外泌体结合形成复合物（A33Ab-US-Exo/Dox），从而靶向 A33 阳性结肠癌细胞。结果表明，A33Ab-US-Exo/Dox 对 LIM1215 细胞具有良好的结合亲和力和抗增殖作用，这是通过复合物的摄取增加来显示的。体内研究表明，A33Ab-US-Exo/Dox 具有优异的肿瘤靶向能力，能够抑制肿瘤生长并延长荷瘤小鼠的生存期，同时降低心脏毒性。总之，通过高密度抗体包被对外泌体进行靶向配体功能化可能被证明是针对人类癌症的靶向药物的新型递药系统。
