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用于在癌细胞中实现可调谐细胞内阿霉素递送的基于双响应性聚(乙烯基己内酰胺)的纳米凝胶

Dual Responsive poly(vinyl caprolactam)-Based Nanogels for Tunable Intracellular Doxorubicin Delivery in Cancer Cells.

作者信息

Rao Kummara Madhusudana, Suneetha Maduru, Kumar Dachuru Vinay, Kim Hyeon Jin, Seok Yong Joo, Han Sung Soo

机构信息

School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, Gyeongbuk, Korea.

Research Institute of Cell Culture, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, Gyeongbuk, Korea.

出版信息

Pharmaceutics. 2022 Apr 13;14(4):852. doi: 10.3390/pharmaceutics14040852.

Abstract

In this work, doxorubicin (Dox)-encapsulated poly(vinyl caprolactam) (PVCL)-based three-dimensional nanogel networks were developed and were crosslinked with disulfide linkages. The nanogels degrade rapidly to low molecular weight chains in the presence of the typical intracellular concentration of glutathione. Doxorubicin (Dox) was successfully encapsulated into these nanogels. The nanogels have a high drug loading of 49% and can be tailored to 182 nm to deliver themselves to the targeted cells and release Dox under dual stimuli conditions, such as redox and temperature. By evaluating cell viability in the HepG2 cell line, we observed that Dox-loaded nanogels effectively killed the cancer cell. Fluorescence microscopy results show that the nanogels could easily be internalized with HepG2 cells. The results confirm that the nanogels destabilized in intracellular cytosol via degradation of disulfide bonds in nanogels networks and release of the Dox nearby the nucleus. These carriers could be promising for cancer drug delivery.

摘要

在这项工作中,开发了基于包载阿霉素(Dox)的聚(乙烯基己内酰胺)(PVCL)的三维纳米凝胶网络,并通过二硫键进行交联。在典型的细胞内谷胱甘肽浓度下,纳米凝胶会迅速降解为低分子量链。阿霉素(Dox)成功封装到这些纳米凝胶中。纳米凝胶具有49%的高载药量,并且可以定制到182nm大小,以便将自身递送至靶细胞,并在氧化还原和温度等双重刺激条件下释放Dox。通过评估HepG2细胞系中的细胞活力,我们观察到载有Dox的纳米凝胶能有效杀死癌细胞。荧光显微镜结果表明,纳米凝胶能够很容易地被HepG2细胞内化。结果证实,纳米凝胶通过纳米凝胶网络中二硫键的降解在细胞内胞质溶胶中不稳定,并在细胞核附近释放Dox。这些载体在癌症药物递送方面可能具有广阔前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53a0/9029372/3075867eb717/pharmaceutics-14-00852-sch001.jpg

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