DOX-loaded pH-sensitive mesoporous silica nanoparticles coated with PDA and PEG induce pro-death autophagy in breast cancer
DOX-loaded pH-sensitive mesoporous silica nanoparticles coated with PDA and PEG induce pro-death autophagy in breast cancer
复制标题
负载 DOX 的 pH 敏感介孔二氧化硅纳米颗粒涂覆 PDA 和 PEG 诱导乳腺癌促死亡自噬
DOI：
10.1039/c7ra05135b
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发表时间：
2017-01-01
期刊：
影响因子：
3.9
通讯作者：
Chen, Hongbo
中科院分区：
文献类型：
--
作者：
Duo, Yanhong;Li, Yang;Chen, Hongbo
开发多功能纳米药物递送载体已成为克服传统化疗药物的药物非选择性、细胞摄取效率低和各种副作用的最有效和普遍的方法之一。在此，我们报道了一种新型负载阿霉素（DOX）的介孔二氧化硅纳米颗粒（MSN），其包覆有聚多巴胺（PDA）和聚乙二醇（PEG）（MSNs-DOX@PDA-PEG），用于治疗乳腺癌。在该系统中，PDA作为pH敏感的看门人，控制MSNs响应pH刺激释放DOX，并且进一步将PEG接枝到PDA表面以增加生理条件下的稳定性和生物相容性。体外释放结果表明MSNs-DOX@PDA-PEG对低pH表现出高敏感性。细胞摄取测定显示，与游离 DOX 相比，MSNs-DOX@PDA-PEG 具有较高的细胞摄取效率。此外，在体内和体外乳腺癌实验中，与游离 DOX 相比，MSNs-DOX@PDA-PEG 还表现出更好的抗癌功效。机制研究表明，与游离 DOX 相比，MSNs-DOX@PDA-PEG 通过抑制 AKT-mTOR-p70S6K 信号通路引起更强的促死亡自噬。综上所述，我们的结果表明，新型材料 MSNs-DOX@PDA-PEG 可能代表一种有前途的乳腺癌治疗纳米制剂。
The development of multifunctional nano drug delivery carriers has been one of the most effective and prevailing approaches to overcome drug non-selectivity, low cell uptake efficiency and various side effects of traditional chemotherapy drugs. Herein, we report a novel doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) coated with polydopamine (PDA) and polyethylene glycol (PEG) (MSNs-DOX@PDA-PEG) for the treatment of breast cancer. In this system, PDA functions as a pH-sensitive gatekeeper to control the release of DOX from MSNs in response to pH-stimulus and PEG was further grafted on the surface of PDA to increase the stability and biocompatibility under physiological conditions. The in vitro release results suggested that MSNs-DOX@PDA-PEG exhibits a high sensitivity to low pH. A cellular uptake assay showed a high cellular uptake efficiency of MSNs-DOX@PDA-PEG compared to free DOX. Furthermore, MSNs-DOX@PDA-PEG also demonstrated an improved anti-cancer efficacy compared to free DOX both in vivo and vitro breast cancer experiments. Mechanistic studies revealed that MSNs-DOX@PDA-PEG causes a stronger pro-death autophagy compared to free DOX via inhibition of the AKT-mTOR-p70S6K signaling pathway. Taken in concert, our results suggest that the novel material MSNs-DOX@PDA-PEG may represent a promising nanoformulation for breast cancer treatment.