Dual-responsive polymer-coated iron oxide nanoparticles for drug delivery and imaging applications.
Dual-responsive polymer-coated iron oxide nanoparticles for drug delivery and imaging applications.
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DOI：
10.1016/j.ijpharm.2014.03.016
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发表时间：
2014-05-15
影响因子：
5.8
通讯作者：
Wadajkar AS
中科院分区：
文献类型：
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作者：
Sundaresan V;Menon JU;Rahimi M;Nguyen KT;Wadajkar AS
我们报道了用于受控和靶向药物输送和成像应用的双响应聚（N-异丙基丙烯酰胺-丙烯酰胺-壳聚糖）（PAC）涂层磁性纳米颗粒（MNP）的合成和表征。 PAC-MNPs尺寸约为150 nm，铁质量含量为70%，具有优异的超顺磁性能。负载抗癌药物阿霉素的 PAC-MNP 表现出双重响应药物释放特性，21 天后，药物最大释放量在 40 °C（~78%）下高于 37 °C（~33%），在 pH 6（~55%）下高于 pH 7.4（~28%）。此外，前列腺癌特异性 R11 肽的缀合增加了前列腺癌 PC3 细胞对 PAC-MNP 的摄取。随着 1.3 T 磁场的存在，纳米粒子的剂量依赖性细胞摄取也显着增加。当与人真皮成纤维细胞和正常前列腺上皮细胞一起孵育 24 小时时，纳米颗粒表现出高达 500 μg/ml 浓度的细胞相容性。最后，药代动力学研究表明，负载阿霉素的 PAC-MNP 在 40°C 时比在 37°C 时引起显着的前列腺癌细胞死亡，从而证实了温度依赖性药物释放动力学和体外治疗功效。未来使用 R11-PAC-MNP 进行靶向图像引导癌症治疗的体内疗效评估将加强多功能 PAC-MNP 对未来药物输送系统的重大影响。
We reported the synthesis and characterization of dual-responsive poly(N-isopropylacrylamide-acrylamide-chitosan) (PAC)-coated magnetic nanoparticles (MNPs) for controlled and targeted drug delivery and imaging applications. The PAC-MNPs size was about 150 nm with 70% iron mass content and excellent superparamagnetic properties. PAC-MNPs loaded with anti-cancer drug doxorubicin showed dual-responsive drug release characteristics with the maximum release of drugs at 40 °C (~78%) than at 37 °C (~33%) and at pH of 6 (~55%) than at pH of 7.4 (~28%) after 21 days. Further, the conjugation of prostate cancer-specific R11 peptides increased the uptake of PAC-MNPs by prostate cancer PC3 cells. The dose-dependent cellular uptake of the nanoparticles was also significantly increased with the presence of 1.3 T magnetic field. The nanoparticles demonstrated cytocompatibility up to concentrations of 500 μg/ ml when incubated over a period of 24 h with human dermal fibroblasts and normal prostate epithelial cells. Finally, pharmacokinetic studies indicated that doxorubicin-loaded PAC-MNPs caused significant prostate cancer cell death at 40 °C than at 37 °C, thereby confirming the temperature-dependent drug release kinetics and in vitro therapeutic efficacy. Future evaluation of in vivo therapeutic efficacy of targeted image-guided cancer therapy using R11-PAC-MNPs will reinforce a significant impact of the multifunctional PAC-MNPs on the future drug delivery systems.