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Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery.
Nanoscale. 2015 Feb 21; 7(7):3137-46.N

Abstract

We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-D-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using a combination of enzymatic transesterification and emulsion copolymerization for intracellular drug delivery. The nanogel exhibited redox, pH and temperature-responsive properties, which can be adjusted by varying the monomer feeding ratio. Furthermore, the volume phase transition temperature (VPTT) of the nanogels was close to body temperature and can result in rapid thermal gelation at 37 °C. Scanning electron microscopy also revealed that the P(ODGal-VCL-MAA) nanogel showed uniform spherical monodispersion. With pyrene as a probe, the fluorescence excitation spectra demonstrated nanogel degradation in response to glutathione (GSH). X-ray diffraction (XRD) showed an amorphous property of DOX within the nanogel, which was used in this study as a model anti-cancer drug. Drug-releasing characteristics of the nanogel were examined in vitro. The results showed multi-responsiveness of DOX release by the variation of environmental pH values, temperature or the availability of GSH, a biological reductase. An in vitro cytotoxicity assay showed a higher anti-tumor activity of the galactose-functionalized DOX-loaded nanogels against human hepatoma HepG2 cells, which was, at least in part, due to specific binding between the galactose segments and the asialoglycoprotein receptors (ASGP-Rs) in hepatic cells. Confocal laser scanning microscopy (CLSM) and flow cytometric profiles further confirmed elevated cellular uptake of DOX by the galactose-functionalised nanogels. Thus, we report here a multi-responsive P(ODGal-VCL-MAA) nanogel with a hepatoma-specific targeting ability for anti-cancer drug delivery.

Authors+Show Affiliations

Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, China. cli0616826@gmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25613320

Citation

Lou, Shaofeng, et al. "Galactose-functionalized Multi-responsive Nanogels for Hepatoma-targeted Drug Delivery." Nanoscale, vol. 7, no. 7, 2015, pp. 3137-46.
Lou S, Gao S, Wang W, et al. Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery. Nanoscale. 2015;7(7):3137-46.
Lou, S., Gao, S., Wang, W., Zhang, M., Zhang, J., Wang, C., Li, C., Kong, D., & Zhao, Q. (2015). Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery. Nanoscale, 7(7), 3137-46. https://doi.org/10.1039/c4nr06714b
Lou S, et al. Galactose-functionalized Multi-responsive Nanogels for Hepatoma-targeted Drug Delivery. Nanoscale. 2015 Feb 21;7(7):3137-46. PubMed PMID: 25613320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery. AU - Lou,Shaofeng, AU - Gao,Shan, AU - Wang,Weiwei, AU - Zhang,Mingming, AU - Zhang,Ju, AU - Wang,Chun, AU - Li,Chen, AU - Kong,Deling, AU - Zhao,Qiang, PY - 2015/1/24/entrez PY - 2015/1/24/pubmed PY - 2015/12/15/medline SP - 3137 EP - 46 JF - Nanoscale JO - Nanoscale VL - 7 IS - 7 N2 - We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-D-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using a combination of enzymatic transesterification and emulsion copolymerization for intracellular drug delivery. The nanogel exhibited redox, pH and temperature-responsive properties, which can be adjusted by varying the monomer feeding ratio. Furthermore, the volume phase transition temperature (VPTT) of the nanogels was close to body temperature and can result in rapid thermal gelation at 37 °C. Scanning electron microscopy also revealed that the P(ODGal-VCL-MAA) nanogel showed uniform spherical monodispersion. With pyrene as a probe, the fluorescence excitation spectra demonstrated nanogel degradation in response to glutathione (GSH). X-ray diffraction (XRD) showed an amorphous property of DOX within the nanogel, which was used in this study as a model anti-cancer drug. Drug-releasing characteristics of the nanogel were examined in vitro. The results showed multi-responsiveness of DOX release by the variation of environmental pH values, temperature or the availability of GSH, a biological reductase. An in vitro cytotoxicity assay showed a higher anti-tumor activity of the galactose-functionalized DOX-loaded nanogels against human hepatoma HepG2 cells, which was, at least in part, due to specific binding between the galactose segments and the asialoglycoprotein receptors (ASGP-Rs) in hepatic cells. Confocal laser scanning microscopy (CLSM) and flow cytometric profiles further confirmed elevated cellular uptake of DOX by the galactose-functionalised nanogels. Thus, we report here a multi-responsive P(ODGal-VCL-MAA) nanogel with a hepatoma-specific targeting ability for anti-cancer drug delivery. SN - 2040-3372 UR - https://www.unboundmedicine.com/medline/citation/25613320/Galactose_functionalized_multi_responsive_nanogels_for_hepatoma_targeted_drug_delivery_ L2 - https://doi.org/10.1039/c4nr06714b DB - PRIME DP - Unbound Medicine ER -