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载紫杉醇的聚乳酸-羟基乙酸纳米粒的间质干细胞用于神经胶质瘤靶向治疗。

Mesenchymal stem cells loaded with paclitaxel-poly(lactic--glycolic acid) nanoparticles for glioma-targeting therapy.

机构信息

Department of Pharmacy, Zhejiang University City College,

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

出版信息

Int J Nanomedicine. 2018 Sep 7;13:5231-5248. doi: 10.2147/IJN.S167142. eCollection 2018.

DOI:10.2147/IJN.S167142
PMID:30237710
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6136913/
Abstract

BACKGROUND: Mesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment. PURPOSE: The objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide--glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats. METHODS: Ptx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection. RESULTS: The optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone. CONCLUSION: Based on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.

摘要

背景：间充质干细胞（MSCs）对肿瘤细胞具有固有趋向性，因此作为胶质瘤治疗的靶向治疗载体引起了越来越多的关注。

目的：本研究旨在证明载紫杉醇（Ptx）的聚（丙交酯-乙交酯）（PLGA）纳米粒（NPs）负载的 MSCs 注射用于大鼠原位胶质瘤治疗。

方法：通过将 MSCs 与 Ptx-PLGA NPs 孵育来获得载 Ptx-PLGA NP 的 MSC。在 Transwell 系统中研究了载 Ptx-PLGA NP 的 MSC 对肿瘤细胞的药物传递和细胞毒性。在对侧注射后，在原位胶质瘤大鼠中评估了药物分布和抗肿瘤活性。

结果：MSC 负载的 Ptx-PLGA NPs 的最佳剂量（1 pg/细胞 Ptx）对 MSC 迁移能力、细胞周期或多谱系分化潜能几乎没有影响。与 Ptx 预处理的 MSCs 相比，Ptx-PLGA NP 预处理的 MSCs 以游离 Ptx 和 Ptx NPs 的形式具有增强的持续 Ptx 释放。MSC 向神经胶质瘤细胞转移 Ptx 可诱导体外肿瘤细胞死亡。就体内分布而言，在治疗性注射后 2 天内，负载 NP 的荧光 MSC 可在整个肿瘤块中追踪到。与单独注射 Ptx 预处理的 MSCs 或 Ptx-PLGA NPs 相比，载 Ptx-PLGA NP 的 MSCs 注射后的存活时间明显延长。

结论：基于 MSC 向肿瘤细胞传递 Ptx 的时间和足够的 Ptx 转移，载 Ptx-PLGA NP 的 MSC 对胶质瘤治疗有效。将载化疗药物的 NPs 纳入 MSCs 是肿瘤靶向治疗的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/11d31e42e72f/ijn-13-5231Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/59bc42cbaa23/ijn-13-5231Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/b83bc560f9d6/ijn-13-5231Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/2d39090d8309/ijn-13-5231Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/41a4e264d288/ijn-13-5231Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/23cd0648e271/ijn-13-5231Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/2622aa8f2aee/ijn-13-5231Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/94ff0eebb106/ijn-13-5231Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/4a70a73cac85/ijn-13-5231Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/4f9af74024a1/ijn-13-5231Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/11d31e42e72f/ijn-13-5231Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/59bc42cbaa23/ijn-13-5231Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/b83bc560f9d6/ijn-13-5231Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/2d39090d8309/ijn-13-5231Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/41a4e264d288/ijn-13-5231Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/23cd0648e271/ijn-13-5231Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/2622aa8f2aee/ijn-13-5231Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/94ff0eebb106/ijn-13-5231Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/4a70a73cac85/ijn-13-5231Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/4f9af74024a1/ijn-13-5231Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6136913/11d31e42e72f/ijn-13-5231Fig10.jpg

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本文引用的文献

[1]
Drug Loaded Gingival Mesenchymal Stromal Cells (GinPa-MSCs) Inhibit In Vitro Proliferation of Oral Squamous Cell Carcinoma.

Sci Rep. 2017-8-24

[2]
Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery.

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Targeted delivery of doxorubicin by nano-loaded mesenchymal stem cells for lung melanoma metastases therapy.

Sci Rep. 2017-3-17

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Stem Cell Res Ther. 2015-8-28

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PLoS One. 2015-6-1

[10]
Clinically applicable human adipose tissue-derived mesenchymal stem cells delivering therapeutic genes to brainstem gliomas.

Cancer Gene Ther. 2015-5-29

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