巨噬细胞输送纳米药物靶向乳腺癌缺氧部位的抗肿瘤活性研究

Nanocarriers crafted to deliver anticancer agents to tumor tissues via passive accumulation through the enhanced permeability and retention effect and active targeting do not show therapeutic efficacy as high as we expected. A critical reason is the nanosystems’ limited penetration into the tumor hypoxic site and thus inaccessibility to the remote tumor cells. Therefore, an ideal nanocarrier maximizing the therapeutic efficacy must simultaneously meet the requirements of deep tumoral penetration, and fast cellular uptake. Herein, we present the macrophage which behaved like a “anti-cancer drug carrier” capable of targeting the tumor hypoxic sites. The macrophage-mediated anti-cancer drug can penetrate deep into tumor hypoxic sites and then control released the active drug, to lead antitumor activity. This new drug delivery system may be a very promising approach uniting the needed properties for high chemotherapeutic efficacy.

针对目前传统纳米药物在肿瘤组织内渗透性差，不能作用于肿瘤深层缺氧部位从而导致疗效改善不明显的问题，本项目以巨噬细胞为研究载体，利用其吞噬能力强及易聚集在肿瘤缺氧区的特性，通过与可控释放型的纳米药物相结合，研究巨噬细胞纳米药物载体的吞噬及释放规律；建立体外缺氧模型以及体内实体瘤模型，探究巨噬细胞介导的纳米药物的缺氧靶向性以及抗肿瘤活性，使其从根本上杀死肿瘤细胞，为纳米药物在提高疗效、降低毒副作用的临床治疗中提供新的思路。

针对目前传统纳米药物在肿瘤组织内渗透性差，不能作用于肿瘤深层缺氧部位从而导致疗效改善不明显的问题，本项目以巨噬细胞为研究载体，利用其吞噬能力强及易聚集在肿瘤缺氧区的特性，进行肿瘤治疗。我们选择巯基乙酸盐诱导的小鼠腹腔巨噬细胞作为生物载体负载 SN38-NPs ，研究巨噬细胞纳米药物载体的吞噬及释放规律；在体外发现此体系对肿瘤细胞有很强的抑制作用，并且在6小时的共孵育过程中对巨噬细胞的毒性较小。建立体内实体瘤模型后，发现其能够直接靶向肿瘤组织，较临床药物CPT-11，表现出较好的抗肿瘤活性，使其从根本上杀死肿瘤细胞。此体系为纳米药物在提高疗效、降低毒副作用的临床治疗中提供新的思路。