pH-Triggered Charge-Reversal Mesoporous Silica Nanoparticles Stabilized by Chitosan Oligosaccharide/Carboxymethyl Chitosan Hybrids for Effective Intracellular Delivery of Doxorubicin
pH-Triggered Charge-Reversal Mesoporous Silica Nanoparticles Stabilized by Chitosan Oligosaccharide/Carboxymethyl Chitosan Hybrids for Effective Intracellular Delivery of Doxorubicin
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DOI：
10.1021/acsabm.8b00830
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发表时间：
2019-05-20
影响因子：
4.7
通讯作者：
Shen, Peihong
中科院分区：
文献类型：
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作者：
Cui, Lan;Liu, Wentao;Shen, Peihong
介孔二氧化硅纳米颗粒(MSN)的表面修饰是提高抗癌药物疗效和降低其毒副作用的有效途径。本工作以氨水/三乙醇胺为催化剂，制得了粒径较小、孔径较大的MSN。针对带负电荷的羧甲基壳聚糖(CMC)和带正电荷的壳寡糖(CS)，设计了pH触发电荷反转CS/CMC双层膜作为MSNS的质子化和去质子化刺激响应开关。结果表明，MSNS-CS/CMC具有核壳结构和介孔结构。在盐酸阿霉素(DOX)的给药过程中，明显观察到表面电荷转换和pH依赖性。细胞内摄取实验表明，DOX@MSNS-CS/CMC可以分布在MCF-7细胞的胞浆中，且毒性较低，与游离DOX和未修饰的DOX@MSNS相比，在pH 7.4时，DOX@MSNS-CS/CMC具有更好的稳定性和更长的滞留时间。此外，在pH 6.5时，DOX@MSNS-CS/CMC的细胞摄取和内化增强，从而促进药物进入细胞核。生物相容性和表面电荷可逆性的MSNS-CS/CMC具有延长血液滞留时间、促进内体逃逸和丰富靶向抗肿瘤策略的潜力，为乳腺癌治疗提供了一个有效的药物输送平台。
Surface modification of mesoporous silica nanoparticles (MSNs) is a promising way to enhance therapeutic efficacy and minimize side effects of anticancer drugs. In this work, MSNs with reduced particle size and optimum pore diameter were obtained and catalyzed by ammonia/triethanolamine. In view of the negatively charged carboxymethyl chitosan (CMC) and positively charged chitosan oligosaccharide (CS), the pH-triggered charge-reversal CS/CMC bilayer was designed as a stimuli-responsive switch for MSNs via the protonation and deprotonation effect. The results showed that MSNs-CS/CMC were core-shell and mesoporous in structure. Surface charge conversion and pH dependence were clearly observed in the doxorubicin hydrochloride (DOX) delivery. The intracellular uptake indicated that DOX@MSNs-CS/CMC could be distributed in the cytoplasm of MCF-7 cells and exhibited lower toxicity, which would improve the stability and prolong the retention time compared to free DOX and unmodified DOX@MSNs at pH 7.4. Moreover, the cellular uptake and internalization of DOX@MSNs-CS/CMC were enhanced to promote drug delivery into the cell nucleus at pH 6.5. The biocompatible and surface-charge-reversible MSNs-CS/CMC have the potential to prolong the retention time in the bloodstream, facilitate the endosome escape, and enrich the targeted antitumor strategy, providing an alternative platform for efficient drug delivery in breast cancer therapy.