First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, Saint-Petersburg, Russian Federation and Nanobiotechnology Laboratory, St Petersburg Academic University, 194021 Saint Petersburg, Russia.
First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, Saint-Petersburg, Russian Federation and Research School of Chemical and Biomedical Engineering, National Research Tomsk Polytechnic University, Lenin Avenue 30, 634050 Tomsk, Russia.
Biomater Sci. 2020 Feb 21;8(4):1137-1147. doi: 10.1039/c9bm00926d. Epub 2019 Oct 4.
Synthetic organic and inorganic carriers often have limitations associated with problematic targeting ability or non-optimized pharmacokinetics, and, therefore, they have restricted therapeutic potential. Natural drug carriers (e.g. mesenchymal stem cells, MSCs) are able to migrate towards the tumor site and penetrate cancerous cells. These biomimetic features make MSCs an attractive delivery platform that allows achieving maximal therapeutic efficiency with minimal toxic side effects. A combination of MSCs exhibiting a homing effect on tumors with stimuli-responsive nanostructured carriers is foreseen to have a huge impact in the field of personalized oncology. Here we develop for the first time a light-sensitive biomimetic delivery platform based on MSCs impregnated with submicron sized composite capsules containing an antitumor drug. This cell-based delivery system triggers the release of the drug upon near-infrared (NIR) laser irradiation due to gold nanorods (Au NRs) incorporated into the capsule wall. The NIR-triggered release of the antitumor drug such as vincristine leads to the effective mortality of tumor spheroids made of primary melanoma cells. Encapsulated vincristine delivered by MSCs into the tumor spheroids and deployed over the whole spheroid upon NIR exposure represents a promising therapy for the improved treatment of malignant neoplasms.
合成有机和无机载体通常具有与靶向能力问题或非优化药代动力学相关的限制，因此，它们的治疗潜力受到限制。天然药物载体（例如间充质干细胞，MSCs）能够迁移到肿瘤部位并穿透癌细胞。这些仿生特性使 MSCs 成为一种有吸引力的递药平台，能够以最小的毒副作用实现最大的治疗效率。预计具有归巢作用的 MSCs 与对刺激有响应的纳米结构载体的结合，将对个性化肿瘤学领域产生巨大影响。在这里，我们首次开发了一种基于负载有载药亚微米复合囊泡的 MSCs 的光响应仿生递药平台。由于胶囊壁中掺入了金纳米棒（Au NRs），这种基于细胞的递药系统在近红外（NIR）激光照射下触发药物释放。阿霉素等抗肿瘤药物的 NIR 触发释放导致由原发性黑素瘤细胞制成的肿瘤球体的有效死亡。MSC 递送至肿瘤球体中的包封阿霉素，并在 NIR 暴露时在整个球体上展开，代表了一种有前途的治疗方法，可改善恶性肿瘤的治疗效果。
