J Biomed Nanotechnol. 2020 Feb 1;16(2):212-223. doi: 10.1166/jbn.2020.2881.
Together with the development of new therapeutic agents, innovation in the delivery system of anti-tumor drugs is required to increase tumor-specificity and avoid unexpected toxicity. To achieve higher efficiency, we combined a live cell-mediated drug delivery system with nanotechnology, with the aim to prove that blood monocytes can be a cargo to deliver antitumor drugs encapsulated in Polymeric poly(D, L-lactide-co-glycolide) acid based nanoparticles (PLGA NPs). In this study, we have characterized how isolated purified monocytes efficiently internalize PLGA-NPs and have imaged their trafficking upon intravenous injection in tumor-bearing mice. Monocytes carrying PLGA-Cy7 NPs were able to reach the tumor site, with superior efficiency than free PLGA-Cy7 NPs, and the bio-distribution analysis confirmed that tumors were the most reached among peripheral tissues. We further demonstrate that monocytes carrying Doxorubicin encapsulated PLGA NPs (PLGA-Doxo) induced strong killing of co-cultured tumor cells. Our studies provide proof-of-concept evidence that monocytes can be exploited in approaches of live cell-mediated drug delivery systems for tumor therapy.
随着新的治疗剂的发展,需要创新抗肿瘤药物的传递系统,以提高肿瘤特异性并避免意外毒性。为了提高效率,我们将活细胞介导的药物传递系统与纳米技术相结合,旨在证明血液单核细胞可以作为携带包裹在基于聚(D,L-丙交酯-共-乙交酯)酸的纳米颗粒(PLGA NPs)中的抗肿瘤药物的载体。在这项研究中,我们描述了分离纯化的单核细胞如何有效地内化 PLGA-NPs,并在荷瘤小鼠中观察了它们在静脉注射后的运输情况。携带 PLGA-Cy7 NPs 的单核细胞能够到达肿瘤部位,其效率优于游离的 PLGA-Cy7 NPs,生物分布分析证实肿瘤是外周组织中最容易到达的部位。我们进一步证明,携带包裹阿霉素的 PLGA NPs(PLGA-Doxo)的单核细胞能够强烈杀伤共培养的肿瘤细胞。我们的研究提供了概念验证证据,表明单核细胞可用于活细胞介导的药物传递系统的肿瘤治疗方法。