Nanoparticle-Laden Macrophages for Tumor-Tropic Drug Delivery.

Nanoparticle-Laden Macrophages for Tumor-Tropic Drug Delivery.
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纳米颗粒巨噬细胞用于肿瘤 - 循环药物递送。

DOI:
10.1002/adma.201805557
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发表时间:
2018-12
期刊:
Advanced materials (Deerfield Beach, Fla.)
影响因子:
--
通讯作者:
Xie J
Xie J
中科院分区:
其他
文献类型:
--
作者:
Zhang W;Wang M;Tang W;Wen R;Zhou S;Lee C;Wang H;Jiang W;Delahunty IM;Zhen Z;Chen H;Chapman M;Wu Z;Howerth EW;Cai H;Li Z;Xie J

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巨噬细胞在癌症药物输送方面具有巨大的潜力,因为它们可以高效地感知趋化线索和肿瘤的发生。然而,在不损害细胞功能的情况下将大量治疗药物装载到巨噬细胞中仍然是一个挑战。在这里,我们报告了一种基于二氧化硅的药物纳米胶囊方法来解决这个问题。我们的纳米胶囊由药物-二氧化硅复合体填充物和固体二氧化硅鞘组成,它的设计是在细胞进入的早期最小限度地释放药物分子。虽然巨噬细胞以高速率摄取纳米胶囊,但在最初的6-12小时内,纳米胶囊对细胞迁移的影响最小,为巨噬细胞在肿瘤中的归宿和药物的原位释放赢得了时间。特别是,我们证明了阿霉素(Dox)作为一种代表性药物,使用这种方法可以负载到高达16.6pg/细胞的巨噬细胞中。在U87 MG异种移植模型上进行测试时,静脉注射(Iv)。注射Dox的巨噬细胞表现出与未经处理的巨噬细胞相似的肿瘤聚集。治疗可以有效地抑制肿瘤生长,同时几乎不会造成全身毒性。我们的研究提出了一种新的选择性药物传递的细胞平台,可以很容易地扩展到其他类型的疾病的治疗。
Macrophages hold great potential in cancer drug delivery because they can sense chemotactic cues and home to tumors with high efficiency. However, it remains a challenge to load large amounts of therapeutics into macrophages without compromising cell functions. Here we report a silica-based drug nanocapsule approach to solve this issue. Our nanocapsule consists of a drug-silica complex filling and a solid silica sheath, and it is designed to minimally release drug molecules in the early hours of cell entry. While taken up by macrophages at high rates, the nanocapsules minimally affect cell migration in the first 6–12 h, buying time for macrophages to home to tumors and release drugs in situ. In particular, we show that doxorubicin (Dox) as a representative drug can be loaded into macrophages up to 16.6 pg/cell using this approach. When tested in a U87MG xenograft model, intravenously (i.v.) injected Dox-laden macrophages show comparable tumor accumulation as untreated macrophages. Therapy leads to efficient tumor growth suppression, while causing little systematic toxicity. Our study suggests a new cell platform for selective drug delivery, which can be readily extended to the treatment of other types of diseases.
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