Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmacy, Fudan University, Shanghai, 201203, China.
J Nanobiotechnology. 2019 Jul 10;17(1):83. doi: 10.1186/s12951-019-0513-z.
Macrophages with tumor-tropic migratory properties can serve as a cellular carrier to enhance the efficacy of anti neoplastic agents. However, limited drug loading (DL) and insufficient drug release at the tumor site remain the main obstacles in developing macrophage-based delivery systems. In this study, we constructed a biomimetic delivery system (BDS) by loading doxorubicin (DOX)-loaded reduced graphene oxide (rGO) into a mouse macrophage-like cell line (RAW264.7), hoping that the newly constructed BDS could perfectly combine the tumor-tropic ability of macrophages and the photothermal property of rGO.
At the same DOX concentration, the macrophages could absorb more DOX/PEG-BPEI-rGO than free DOX. The tumor-tropic capacity of RAW264.7 cells towards RM-1 mouse prostate cancer cells did not undergo significant change after drug loading in vitro and in vivo. PEG-BPEI-rGO encapsulated in the macrophages could effectively convert the absorbed near-infrared light into heat energy, causing rapid release of DOX. The BDS showed excellent anti-tumor efficacy in vivo.
The BDS that we developed in this study had the following characteristic features: active targeting of tumor cells, stimuli-release triggered by near-infrared laser (NIR), and effective combination of chemotherapy and photothermotherapy. Using the photothermal effect produced by PEG-BPEI-rGO and DOX released from the macrophages upon NIR irradiation, MAs-DOX/PEG-BPEI-rGO exhibited a significant inhibitory effect on tumor growth.
具有肿瘤趋向迁移特性的巨噬细胞可以作为细胞载体,增强抗肿瘤药物的疗效。然而,在肿瘤部位的药物负载(DL)有限和药物释放不足仍然是开发基于巨噬细胞的递药系统的主要障碍。在这项研究中,我们通过将载多柔比星(DOX)的还原氧化石墨烯(rGO)加载到鼠巨噬细胞样细胞系(RAW264.7)中构建了仿生递药系统(BDS),希望新构建的 BDS 能够完美结合巨噬细胞的肿瘤趋向能力和 rGO 的光热特性。
在相同的 DOX 浓度下,巨噬细胞比游离 DOX 吸收更多的 DOX/PEG-BPEI-rGO。RAW264.7 细胞对 RM-1 小鼠前列腺癌细胞的肿瘤趋向能力在体外和体内载药后没有明显变化。包封在巨噬细胞中的 PEG-BPEI-rGO 可以有效地将吸收的近红外光转化为热能,导致 DOX 的快速释放。BDS 在体内表现出优异的抗肿瘤疗效。
我们在这项研究中开发的 BDS 具有以下特点:肿瘤细胞的主动靶向、近红外激光(NIR)触发的刺激释放以及化学治疗和光热治疗的有效结合。利用 PEG-BPEI-rGO 产生的光热效应和巨噬细胞在 NIR 照射下释放的 DOX,MA-DOX/PEG-BPEI-rGO 对肿瘤生长表现出显著的抑制作用。