Thermoresponsive nanocomposite gel for local drug delivery to suppress the growth of glioma by inducing autophagy
Thermoresponsive nanocomposite gel for local drug delivery to suppress the growth of glioma by inducing autophagy
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用于局部药物递送的热响应纳米复合凝胶通过诱导自噬抑制神经胶质瘤的生长
DOI：
10.1080/15548627.2017.1320634
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发表时间：
2017-01-01
期刊：
影响因子：
13.3
通讯作者：
Duan, Yourong
中科院分区：
文献类型：
--
作者：
Ding, Li;Wang, Qi;Duan, Yourong
恶性脑胶质瘤的治疗方法包括手术、放疗和口服药物化疗，但其预后仍很差。我们开发了聚乙二醇-二棕榈酰磷脂酰乙醇胺（mPEG-DPPE）磷酸钙纳米颗粒（NPs）可注射温敏性水凝胶（纳米复合凝胶），其可以提供紫杉醇（PTX）和替莫唑胺（TMZ）的持续和局部递送。此外，通过Chou和Talalay方法确定PTX和TMZ对C6细胞的最佳协同抗胶质瘤作用的比例为1：100（w/w）。我们的结果清楚地表明，PTX：TMZ NPs诱导的自噬在调节肿瘤细胞死亡中起重要作用，而自噬抑制显著逆转PTX：TMZ NPs的抗肿瘤作用，表明抗增殖自噬响应于PTX：TMZ NPs处理而发生。使用C6荷瘤大鼠原位评价PTX：TMZ NP负载凝胶的抗肿瘤功效，并且PTX：TMZ NP负载凝胶表现出上级抗肿瘤性能。在这项研究中，纳米复合物凝胶在体内的抗肿瘤作用与自噬细胞死亡相关。体内结果进一步证实了这种策略的优点。本研究为纳米药物的临床应用提供了依据。
ABSTRACT Although the treatments of malignant glioma include surgery, radiotherapy and chemotherapy by oral drug administration, the prognosis of patients with glioma remains very poor. We developed a polyethylene glycol-dipalmitoylphosphatidyle- thanoiamine (mPEG-DPPE) calcium phosphate nanoparticles (NPs) injectable thermoresponsive hydrogel (nanocomposite gel) that could provide a sustained and local delivery of paclitaxel (PTX) and temozolomide (TMZ). In addition, the proportion of PTX and TMZ for the optimal synergistic antiglioma effect on C6 cells was determined to be 1:100 (w/w) by the Chou and Talalay method. Our results clearly indicated that the autophagy induced by PTX:TMZ NPs plays an important role in regulating tumor cell death, while autophagy inhibition dramatically reverses the antitumor effect of PTX:TMZ NPs, suggesting that antiproliferative autophagy occurs in response to PTX:TMZ NPs treatment. The antitumor efficacy of the PTX:TMZ NP-loaded gel was evaluated in situ using C6 tumor-bearing rats, and the PTX:TMZ NP-loaded gel exhibited superior antitumor performance. The antitumor effects of the nanocomposite gel in vivo were shown to correlate with autophagic cell death in this study. The in vivo results further confirmed the advantages of such a strategy. The present study may provide evidence supporting the development of nanomedicine for potential clinical application.