Controlled release of cisplatin from pH-thermal dual responsive nanogels
Controlled release of cisplatin from pH-thermal dual responsive nanogels
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DOI：
10.1016/j.biomaterials.2013.07.092
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发表时间：
2013-11-01
期刊：
影响因子：
14
通讯作者：
Qian, Zhiyong
中科院分区：
文献类型：
--
作者：
Peng, Jinrong;Qi, Tingting;Qian, Zhiyong
在这项研究中，一种ph -热双响应纳米凝胶被应用于顺铂（CDDP）的递送。CDDP通过与纳米凝胶中的羧基结合而被加载到纳米凝胶中。并用FTIR和XPS对其偶联进行了验证。CDDP和COOH之间的键可以被H+或Cl-破坏。我们发现CDDP在更酸性的环境中释放得更快。纳米系统在人体内的Cl-浓度约为95 ~ 105 mM，在注入体内时，共轭键容易受到Cl-的攻击。为了减少Cl-触发CDDP从纳米凝胶中释放，我们在纳米凝胶结构中引入了热响应单元- nipam。引入NIPAm后，在pH = 7.38的缓冲液中，在Cl- (150 mu)的存在下，CDDP在37℃下从纳米凝胶中释放的速度比没有NIPAm的纳米凝胶慢得多。通过体外释放行为研究，我们发现含NIPAm纳米凝胶的CDDP在37℃下的释放速度比在25℃下的释放速度慢，H+的攻击可以加速CDDP的释放，温度升高则可以降低CDDP的释放速度。通过细胞摄取观察，我们发现纳米凝胶主要定位于癌细胞的细胞质中。与游离CDDP相比，负载CDDP的纳米凝胶在体内循环时间更长。在小鼠体内治疗乳腺癌模型中，其抗癌性能优于游离CDDP。此外，纳米凝胶的负载也减少了CDDP的一些副作用，如肾毒性、静脉炎、骨髓抑制等。体外和体内实验结果表明，该双责任纳米凝胶是一种合适的CDDP递送候选材料。(C) 2013 Elsevier Ltd.版权所有。
In this study, a pH-thermal dual responsive nanogel was applied for cisplatin (CDDP) delivery. CDDP was loaded into the nanogels via conjugation with the carboxyl groups in the nanogels. The conjugation was confirmed by FTIR and XPS. The bonding between CDDP and COOH can be broken by the H+ or Cl-. We found that the CDDP released much faster at more acidic environment. The Cl- concentration in the human body is about 95-105 mM. The conjugated bond could be easily attacked by Cl- while the nanosystem is injected into the body. In order to diminish the Cl- triggering release of CDDP from the nanogels, we introduced a thermal-responsive units-NIPAm into the nanogel structure. After NIPAm introduced, the CDDP released much slower from the nanogels at 37 degrees C in pH = 7.38 buffer in the present of Cl- (150 mu) than that without NIPAm. And the CDDP also released slower from the nanogels at 37 degrees C than at 25 degrees C. By in vitro release behavior studying, we found that CDDP release from the NIPAm containing nanogels can be accelerated by H+ attacking and reduced by temperature arising. By cellular uptake observation, we found that the nanogels were mainly localized in the cytoplasm of the cancer cells. The CDDP-loaded nanogels exhibited longer circulation time in vivo while compared to free CDDP. And it has better anti-cancer performance than free CDDP in vivo therapy of breast cancer in mice model. Furthermore, some side effects of CDDP, such as renal toxicity, phlebitis, bone marrow suppression etc. have also been reduced by nanogels loading. The in vitro and in vivo results demonstrated that the dual responsible nanogel is a suitable CDDP delivery candidate. (C) 2013 Elsevier Ltd. All rights reserved.