Matai Ishita, Gopinath P
Nanobiotechnology Laboratory, Centre for Nanotechnology, and ‡Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
Nanobiotechnology Laboratory, Centre for Nanotechnology, and Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
ACS Biomater Sci Eng. 2016 Feb 8;2(2):213-223. doi: 10.1021/acsbiomaterials.5b00392. Epub 2016 Jan 12.
Proper choice and design of nanocarriers is imperative to achieve the desired therapeutic benefits. Herein, we report a facile methodology for preparation of chemically cross-linked AG-G5 hybrid nanogels of alginate (AG) and G5.0 poly(amidoamine) (PAMAM) dendrimer via carbodiimide chemistry. The rationale behind the formulation of AG-G5 nanogels is to attain effective and sustained delivery of chemotherapeutic agents. Physical entrapment of anticancer drug epirubicin (EPI) within AG-G5 nanogels endows them with therapeutic properties. Analytical techniques such as zeta potential (ζ) measurements, field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) confirm the integration of PAMAM dendrimer with alginate structure. Thermal, swelling studies, and surface area estimations suggest improved stability and porosity of AG-G5 nanogels. Moreover, AG-G5 nanogels exhibited significantly better mechanical properties and pH dependent release of EPI than AG nanogels. Fluorescence microscopy, cell viability assay, cell cycle analysis and FE-SEM imaging indicated apoptosis inducing potential of EPI⊂AG-G5 nanogels by enhanced intracellular EPI accumulation in breast cancer (MCF-7) cells. Overall, our results put forth AG-G5 hybrid nanogels as prospective candidates to achieve enhanced anticancer effects in vitro.
为实现预期的治疗效果，纳米载体的正确选择和设计至关重要。在此，我们报告了一种简便的方法，通过碳二亚胺化学法制备藻酸盐（AG）和G5.0聚酰胺胺（PAMAM）树枝状大分子的化学交联AG-G5杂化纳米凝胶。AG-G5纳米凝胶配方背后的基本原理是实现化疗药物的有效和持续递送。将抗癌药物表柔比星（EPI）物理包裹在AG-G5纳米凝胶中赋予了它们治疗特性。诸如zeta电位（ζ）测量、场发射扫描电子显微镜（FE-SEM）、透射电子显微镜（TEM）和傅里叶变换红外光谱（FTIR）等分析技术证实了PAMAM树枝状大分子与藻酸盐结构的整合。热学、溶胀研究和表面积估计表明AG-G5纳米凝胶的稳定性和孔隙率得到了改善。此外，AG-G5纳米凝胶在机械性能和EPI的pH依赖性释放方面表现出比AG纳米凝胶明显更好的性能。荧光显微镜、细胞活力测定、细胞周期分析和FE-SEM成像表明，EPI⊂AG-G5纳米凝胶通过增强乳腺癌（MCF-7）细胞内EPI的积累具有诱导凋亡的潜力。总体而言，我们的结果提出AG-G5杂化纳米凝胶作为在体外实现增强抗癌效果的潜在候选物。
