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Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach.
Int J Nanomedicine. 2017; 12:3653-3664.IJ

Abstract

A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an "arm-first" atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy.

Authors+Show Affiliations

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University.Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People's Republic of China.Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People's Republic of China.Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University.Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People's Republic of China.Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University.Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People's Republic of China.Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University. Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28553105

Citation

Lou, Shaofeng, et al. "Preparation of a Dual Cored Hepatoma-specific Star Glycopolymer Nanogel Via Arm-first ATRP Approach." International Journal of Nanomedicine, vol. 12, 2017, pp. 3653-3664.
Lou S, Zhang X, Zhang M, et al. Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach. Int J Nanomedicine. 2017;12:3653-3664.
Lou, S., Zhang, X., Zhang, M., Ji, S., Wang, W., Zhang, J., Li, C., & Kong, D. (2017). Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach. International Journal of Nanomedicine, 12, 3653-3664. https://doi.org/10.2147/IJN.S134367
Lou S, et al. Preparation of a Dual Cored Hepatoma-specific Star Glycopolymer Nanogel Via Arm-first ATRP Approach. Int J Nanomedicine. 2017;12:3653-3664. PubMed PMID: 28553105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach. AU - Lou,Shaofeng, AU - Zhang,Xiuyuan, AU - Zhang,Mingming, AU - Ji,Shenglu, AU - Wang,Weiwei, AU - Zhang,Ju, AU - Li,Chen, AU - Kong,Deling, Y1 - 2017/05/11/ PY - 2017/5/30/entrez PY - 2017/5/30/pubmed PY - 2017/9/20/medline KW - arm-first ATRP KW - drug delivery KW - glycopolymer KW - hepatoma targeting KW - multi-responsive nanogel SP - 3653 EP - 3664 JF - International journal of nanomedicine JO - Int J Nanomedicine VL - 12 N2 - A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an "arm-first" atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy. SN - 1178-2013 UR - https://www.unboundmedicine.com/medline/citation/28553105/Preparation_of_a_dual_cored_hepatoma_specific_star_glycopolymer_nanogel_via_arm_first_ATRP_approach_ L2 - https://dx.doi.org/10.2147/IJN.S134367 DB - PRIME DP - Unbound Medicine ER -