【奥思达前沿科技】ACS Nano：纳米粒子靶向杀死癌症干细胞

许多癌症患者在疾病治疗后仅在几年之内就会肿瘤复发。肿瘤复发和扩散很可能是由于传统抗癌药物很难杀死肿瘤干细胞造成的。现在，研究人员设计的一种纳米粒子可专门针对这些肿瘤干细胞释放药物。有关纳米粒子疗法的相关文章发表在《ACS Nano》杂志上。

抗癌药物通常可以使肿瘤组织萎缩，但不会杀死肿瘤干细胞(CSCs)。尽管肿瘤干细胞在肿瘤组织中可能只占一小部分，但其抗药性使它们能够持续在体内存活。肿瘤干细胞可以引发肿瘤再生或使癌细胞扩散到全身。研究者们预想开发一种纳米粒子系统来攻克这些肿瘤干细胞的防御机制。

研究人员将抗癌药物阿霉素置入涂有壳聚糖的纳米粒子中，壳聚糖是一种天然的多糖类物质，可专门用于肿瘤干细胞。一旦肿瘤处于酸性环境中，纳米粒子就会退化并释放药物。有关内容的测试是一种小型的体外正常组织和肿瘤干细胞的测试。本项测试中，小鼠体内人类乳腺肿瘤组织的生长情况显示该治疗方法成功的杀死了肿瘤干细胞并清除了肿瘤组织。经实验观察，小鼠没有明显的副作用。该研究资金来自美国癌症协会和Pelotonia。

doi:10.1021/nn506928p

PMID:

Chitosan-Decorated Doxorubicin-Encapsulated Nanoparticle Targets and Eliminates Tumor Reinitiating Cancer Stem-like Cells

Wei Rao, Hai Wang, Jianfeng Han, Shuting Zhao, Jenna Dumbleton, Pranay Agarwal, Wujie Zhang, Gang Zhao, Jianhua Yu, Debra L. Zynger, Xiongbin Lu, Xiaoming He.

Tumor reinitiating cancer stem-like cells are responsible for cancer recurrence associated with conventional chemotherapy. We developed a doxorubicin-encapsulated polymeric nanoparticle surface-decorated with chitosan that can specifically target the CD44 receptors of these cells. This nanoparticle system was engineered to release the doxorubicin in acidic environments, which occurs when the nanoparticles are localized in the acidic tumor microenvironment and when they are internalized and localized in the cellular endosomes/lysosomes. This nanoparticle design strategy increases the cytotoxicity of the doxorubicin by six times in comparison to the use of free doxorubicin for eliminating CD44+ cancer stem-like cells residing in 3D mammary tumor spheroids (i.e., mammospheres). We further show these nanoparticles reduced the size of tumors in an orthotopic xenograft tumor model with no evident systemic toxicity. The development of nanoparticle system to target cancer stem-like cells with low systemic toxicity provides a new treatment arsenal for improving the survival of cancer patients.

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