Red blood cell-derived nanovesicles for safe and efficient macrophage-targeted drug delivery in vivo
Red blood cell-derived nanovesicles for safe and efficient macrophage-targeted drug delivery in vivo
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红细胞衍生的纳米囊泡可用于体内安全有效的巨噬细胞靶向药物递送
DOI：
10.1039/c8bm01258j
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发表时间：
2019-01-01
影响因子：
6.6
通讯作者：
Sun, Tianmeng
中科院分区：
文献类型：
--
作者：
Wan, Xue;Zhang, Shi;Sun, Tianmeng
巨噬细胞靶向给药在癌症和炎症性疾病的治疗中具有巨大的治疗潜力。还存在对体内巨噬细胞消耗的有效且无毒的手段的未满足的需求，以确定巨噬细胞在正常和疾病环境下的作用。在此，我们探索了红细胞（RBC）衍生的纳米囊泡（RDNV）作为药物纳米载体特异性消耗巨噬细胞的潜力。我们表明，RDNVs是有效的亲水性药物载体，可以有效地将药物输送到巨噬细胞在体外和体内。来源于野生型小鼠RBC（WT-RDNV）和CD 47 KO小鼠RBC（KO-RDNV）的纳米囊泡可以包封氯膦酸盐，在PBS中具有良好的稳定性，用于长期储存。然而，KO-RDNV在体外更有效地被巨噬细胞吞噬，并且在体内比WT-RDNV更快速地清除，表明CD 47也作为RDNV的不吃我分子，就像它对于RBC一样。因此，氯膦酸盐包封的KO-RDNV（KO-RDNV/CLD）在体外对小鼠巨噬细胞的毒性显著高于载药的WT-RDNV（WT-RDNV/CLD）。此外，WT-RDNV/CLD显示在组织（例如，肝和肺）和巨噬细胞消耗对比KO-RDNV/CLD。重要的是，RBC衍生的纳米囊泡在体内比氯膦酸盐包封的脂质体（目前的金标准巨噬细胞消耗试剂）更具生物相容性且毒性更低。本研究为巨噬细胞靶向给药提供了一个有用的策略。
Macrophage-targeted drug delivery has great therapeutic potential for the treatment of cancers and inflammatory diseases. There is also an unmet need for efficient and nontoxic means of in vivo macrophage depletion to determine the role of macrophages under normal and disease settings. Herein, we explored the potential of red blood cell (RBC)-derived nanovesicles (RDNVs) as drug nanocarriers to specifically deplete macrophages. We show that RDNVs are effective hydrophilic drug carriers and can effectively deliver drugs into macrophages both in vitro and in vivo. Nanovesicles derived from both wild-type mouse RBCs (WT-RDNVs) and CD47 KO mouse RBCs (KO-RDNVs) can encapsulate clodronate with good stability in PBS for long-term storage. However, KO-RDNVs were more efficiently engulfed by macrophages in vitro and more rapidly cleared in vivo than WT-RDNVs, indicating that CD47 also serves as a don't eat me molecule for RDNVs as it does for RBCs. Accordingly, clodronate-encapsulated KO-RDNVs (KO-RDNV/CLD) were significantly more toxic to mouse macrophages in vitro than drug-loaded WT-RDNVs (WT-RDNV/CLD). Furthermore, WT-RDNV/CLD showed prolonged accumulation in tissues (e.g., liver and lung) and macrophage depletion versus KO-RDNV/CLD. Importantly, RBC-derived nanovesicles are more biocompatible and less toxic in vivo than clodronate-encapsulated liposomesthe current gold-standard macrophage-depleting reagent. This study offers a useful strategy for macrophage-targeted drug delivery.