Novel silk fibroin nanoparticles incorporated silk fibroin hydrogel for inhibition of cancer stem cells and tumor growth.
Novel silk fibroin nanoparticles incorporated silk fibroin hydrogel for inhibition of cancer stem cells and tumor growth.
复制标题
新型丝素蛋白纳米粒子掺入丝素蛋白水凝胶，可抑制癌症干细胞和肿瘤生长。
DOI：
10.2147/ijn.s166104
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发表时间：
2018
影响因子：
8
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Wu P;Liu Q;Wang Q;Qian H;Yu L;Liu B;Li R
由于癌症的肿瘤内异质性导致不同的药物敏感性，因此需要多药物递送平台。癌症干细胞（CSC）是负责肿瘤接种和复发的一小群肿瘤细胞，被认为是化疗抗性的，并且已报道对盐霉素（Sal）而不是紫杉醇（Ptx）敏感。在这里，我们报告了一种新的丝素蛋白（SF）水凝胶加载Sal和Ptx通过纳入载药丝素蛋白纳米粒子（SF-NPs），同时杀死CSC和非CSC。使用我们先前报道的制备Ptx-SF-NPs（Ptx-SF-NPs）的方法，在温和且无毒的条件下制备Sal-SF-NPs（Sal-SF-NPs）。在凝胶化之前，将载药的SF-NP分散在超声处理的SF溶液中。所得SF水凝胶（Sal-Ptx-NP-凝胶）与未掺入NP的水凝胶相比保留其可注射性质，表现出生物可降解性并证明了均匀的药物分布。在小鼠肝癌H22皮下肿瘤模型中，Sal-Ptx-NP-凝胶显示出优于单载药水凝胶和全身性双重药物给药的肿瘤生长抑制。Sal-Ptx-NP-凝胶还显著减少了CD 44 + CD 133+肿瘤细胞，并在体内肿瘤接种实验中显示出最少的肿瘤形成，表明对癌症干细胞的上级抑制。这些结果表明，SF-NPs掺入SF水凝胶是一种有前途的药物递送平台，Sal-Ptx-NP-Gel可能是一种新的和强大的局部肿瘤治疗方案在未来。
A multi-drug delivery platform is needed as the intra-tumoral heterogeneity of cancer leads to different drug susceptibility. Cancer stem cells (CSCs), a small population of tumor cells responsible for tumor seeding and recurrence, are considered chemotherapy-resistant and have been reported to be sensitive to salinomycin (Sal) instead of paclitaxel (Ptx). Here we report a novel silk fibroin (SF) hydrogel-loading Sal and Ptx by incorporating drug-loaded silk fibroin nanoparticles (SF-NPs) to simultaneously kill CSCs and non-CSCs. Using the method we have previously reported to prepare Ptx-loaded SF-NPs (Ptx-SF-NPs), Sal-loaded SF-NPs (Sal-SF-NPs) were fabricated under mild and non-toxic conditions. The drug-loaded SF-NPs were dispersed in the ultrasound processed SF solution prior to gelation. The resulting SF hydrogel (Sal-Ptx-NP-Gel) retained its injectable properties, exhibited bio-degradability and demonstrated homogeneous drug distribution compared to the non-NP incorporated hydrogel. Sal-Ptx-NP-Gel showed superior inhibition of tumor growth compared to single drug-loaded hydrogel and systemic dual drug administration in the murine hepatic carcinoma H22 subcutaneous tumor model. Sal-Ptx-NP-Gel also significantly reduced CD44+CD133+ tumor cells and demonstrated the least tumor formation in the in vivo tumor seeding experiment, indicating superior inhibition of cancer stem cells. These results suggest that SF-NPs incorporated SF hydrogel is a promising drug delivery platform, and Sal-Ptx-NP-Gel could be a novel and powerful locoregional tumor treatment regimen in the future.