Nanoparticles made from membrane of mesenchymal stem cells (MSCs) showed active targeting capacities to prostate and lung cancers, but further studies are hindered by limited expandability and donor variations of tissue-derived MSCs. We have derived MSCs with an unlimited supply and uniform homing capacity to triple-negative breast cancer (TNBC) from human induced pluripotent stem cells (iPSCs). By breaking down intact iPSC-MSCs, we efficiently developed nanovesicles that selectively accumulated in primary and metastatic TNBC after systemic infusion in mouse models. When loaded with a chemotherapeutic drug doxorubicin, iPSC-MSC nanovesicles showed superior cytotoxic effects on doxorubicin-resistant TNBC cells, and significantly decreased the incidence and burden of metastases in mouse models of spontaneous and experimental metastatic TNBC compared with free or liposomal doxorubicin. These nanovesicles showed no detectable immunogenicity or toxicity, and are stable after storage. Our data indicate that iPSC-MSC nanovesicles are promising to improve TNBC treatment as a standardized targeting platform.

中文翻译：

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由iPS细胞衍生的间充质干细胞制成的仿生纳米囊泡，用于三阴性乳腺癌的靶向治疗。

由间充质干细胞（MSCs）的膜制成的纳米颗粒显示出对前列腺癌和肺癌的有效靶向能力，但是由于组织衍生的MSCs的有限的可扩展性和供体变异而阻碍了进一步的研究。我们已经从人诱导的多能干细胞（iPSC）中获得了对三阴性乳腺癌（TNBC）具有无限供应和统一归巢能力的MSC。通过分解完整的iPSC-MSC，我们有效地开发出了纳米囊泡，在小鼠模型中进行系统性输注后，该囊泡选择性地积聚在主要和转移性TNBC中。当载有化疗药物阿霉素时，iPSC-MSC纳米囊泡对耐阿霉素的TNBC细胞表现出优异的细胞毒性作用，与游离或脂质体阿霉素相比，在自发性和实验性转移TNBC小鼠模型中转移的发生率和负担显着降低。这些纳米囊泡没有显示出可检测的免疫原性或毒性，并且在储存后是稳定的。我们的数据表明，iPSC-MSC纳米囊泡有望作为标准的靶向平台改善TNBC的治疗。