Title
Cell-targeted, dual reduction- and pH-responsive saccharide/lipoic acid-modified poly(L-lysine) and poly(acrylic acid) polyionic complex nanogels for drug delivery
Author
Su-Chun How, Yu-Fon Chen, Pin-Lun Hsieh, Steven, S.-S. Wang, Jeng-Shiung Jan
Year
2017
Journal
Colloids and Surfaces B: Biointerfaces
Abstract
A cell-targeted, reduction-/pH-responsive polyionic complex (PIC) nanogel system was developed by simply mixing cationic lactobionolatone/lipoic acid-modified poly(L-lysine) (PLL-g-(Lipo–Lac)) and anionic poly(acrylic acid) (PAA), followed by disulfide cross-linking. The nanogels with sizes smaller than 150 nm can be prepared at certain mixing ratio via forming interchain disulfide cross-link and helical PAA/PLL complexes. In vitro drug release study showed that Doxorubicin (Dox) release from the nanogels was significantly enhanced by increasing acidity and/or introducing disulfide cleaving agent. Carbohydrate-lectin binding and cellular uptake studies confirmed that Lac-conjugated nanogels can effectively bind to the cells bearing asialoglycoprotein receptors and subsequently afford efficient cell internalization. Cytotoxicity assays showed that Dox-loaded, Lac-conjugated nanogels exhibited efficient cell proliferation inhibition toward HepG2 cells, whereas the nanogels exhibited excellent biocompatibility. Furthermore, TUNEL assay was employed to detect apoptosis pertaining to the mechanism of cell death. This study highlights that polyionic complexation with subsequent cross-linking can be a simple approach to prepare multifunctional nanogels as drug delivery vehicles.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Materials, Biochemistry