title: Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery.
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.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin 300192, China. cli0616826@gmail.com.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Lou
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D001212:Asialoglycoproteins / Q000737:chemistry; D001412:Bacillus subtilis / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry; D001831:Body Temperature; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004952:Esters; D005434:Flow Cytometry; D005690:Galactose / Q000737:chemistry; D005782:Gels; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology; D010084:Oxidation-Reduction; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D001212:Asialoglycoproteins; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D004952:Esters; D005782:Gels; D005978:Glutathione; D005690:Galactose