School of Physical Sciences, Jawaharlal Nehru University, New Delhi, India.
School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.
Int J Biol Macromol. 2020 Jun 1;152:1027-1037. doi: 10.1016/j.ijbiomac.2019.10.190. Epub 2019 Nov 19.
Herein, we report pH-responsive hydrogels of hierarchically self-assembled protein (zein, in the form of its nanoparticles of size 80-120 nm) and polysaccharide (pectin), where gelation occurred below pH 3 in the absence of crosslinkers, which we used for encapsulation and release of anticancer drug, Doxorubicin (DOX) in the cell nucleus. These nanoparticles, spherical in shape, in addition to helping in the formation of gel network also encapsulate the drug and pectin layer adsorbed on the surface of these nanoparticle allows for the drying, redispersion and enhanced swelling. A monovalent salt-dependent study performed in the concentration range of 1-100 mM clearly showed the associative interaction between the zein nanoparticles and pectin chains were hydrophobic in nature. FTIR results confirmed the loading of the drug inside the nanoparticles. Melting profile studies of these gels revealed that encapsulation of drug did not change the thermo-physical properties. Doxorubicin drug loaded hydrogels exhibited superior cytotoxicity towards cervical cancer cell lines by inducing intracellular-antioxidative stress-based apoptosis. Confocal microscopy revealed that the hydrogels required quite less time of 4 h to completely penetrate the cells assisted by the charge specific electrostatic interaction between the negatively charged HeLa cells and positively charged crosslinks. The data, further revealed that these pH specific hydrogels were suitable for release of the drug in cell nucleus is assisted by the acidic environment of cellular organelles, and hence have a potential in cancer therapy with minimal collateral damage to healthy cells.
本文报道了一种具有分级自组装特性的蛋白（玉米醇溶蛋白，以粒径为 80-120nm 的纳米颗粒形式存在）和多糖（果胶）的 pH 响应水凝胶。在没有交联剂的情况下，低于 pH 3 时即可发生凝胶化，我们将其用于封装和释放抗癌药物阿霉素（DOX）到细胞核中。这些纳米颗粒呈球形，不仅有助于形成凝胶网络，还可以包裹药物，并且吸附在这些纳米颗粒表面的果胶层允许其进行干燥、再分散和增强溶胀。在 1-100mM 的浓度范围内进行的单价盐依赖性研究清楚地表明，玉米醇溶蛋白纳米颗粒与果胶链之间存在的是疏水相互作用。FTIR 结果证实了药物已被负载到纳米颗粒内部。这些凝胶的熔融曲线研究表明，药物的包封并未改变其热物理性质。载有阿霉素的水凝胶通过诱导细胞内抗氧化应激相关的细胞凋亡，对宫颈癌细胞系表现出优异的细胞毒性。共聚焦显微镜揭示，这些带电荷的水凝胶在正电荷交联剂的帮助下，仅需 4 小时即可完全穿透细胞，这归因于带负电荷的 HeLa 细胞与带正电荷的交联剂之间的静电相互作用。进一步的数据表明，这些 pH 响应性水凝胶在细胞器的酸性环境的辅助下，非常适合在细胞核中释放药物，因此在癌症治疗方面具有潜力，对健康细胞的副作用最小。
