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.

Saccharide‐based nanocarriers for targeted therapeutic and diagnostic applications

“…The nanogel exhibited triple responsiveness to redox, pH and temperature stimuli, which could be tuned by varying the monomer feed ratio. Similarly, the nanogels showed superior performance in a cytotoxicity assay against human hepatoma HepG2 cells, which was in part due to the specific targeting of ASGP‐Rs …”

Intelligent micellar polymeric nanocarriers for therapeutics and diagnosis

“…As such, the tripeptide Arg–Gly–Asp (RGD) can bind to the α ν β 3 integrin receptor, which is largely expressed at the surface of malignant cells and in tumor‐proliferating neovascular endothelial cells . Carbohydrates bind specifically to the asialoglycoprotein receptors commonly found in liver cells . Micelles with surface‐attached antibodies, known as immunomicelles, provide a wide variety of targets and specificity of interactions while retaining the ability of antibodies to specifically interact with their antigens as, for example, in the case of radiolabeled trastuzumab (TmAb)‐decorated [Fab fraction (TmAb–Fab)]–PEG–PCL micelles, which show an enhanced accumulation and site‐specific localization in mice bearing subcutaneous human epidermal growth factor receptor 2 (HER2) positive BT‐474 tumors, as observed by micro‐single‐photon emission tomography–computing tomography (Figure ) .…”

Perspectives on the Emerging Applications of Multifaceted Biomedical Polymeric Nanomaterials

“…Additionally, using confocal laser scanning microscopy, the researchers were able to demonstrate the effectiveness of the NIR irradiation in triggering the DOX release from the nanogel, thus causing a significant level of cytotoxicity to HeLa cells [116]. In a similar study, a combination of enzymatic transesterification and emulsion copolymerization was employed to prepare poly-galactose-functionalized multiresponsive nanogels for hepatoma-targeted drug delivery [117]. Similar to this study too, Qin et al [116] employed the use of confocal laser scanning microscopy and flow cytometry to establish the elevated cellular uptake of DOX encapsulated in the functionalized nanogels.…”