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.
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 150nm 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.
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: How
authors.affiliation: Department of Chemical Engineering, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yu-Fon
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Pin-Lun
authors.initials: PL
authors.lastname: Hsieh
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan. Electronic address: sswang@ntu.edu.tw.
authors.forename: Steven S-S
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering, National Cheng Kung University, Tainan 701, Taiwan. Electronic address: jsjan@mail.ncku.edu.tw.
authors.forename: Jeng-Shiung
authors.initials: JS
authors.lastname: Jan
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002241:Carbohydrates / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020287:In Situ Nick-End Labeling; D051379:Mice; D000080385:Nanogels; D010084:Oxidation-Reduction; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D008063:Thioctic Acid / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D000903:Antibiotics, Antineoplastic; D002241:Carbohydrates; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011107:Polylysine; D011092:Polyethylene Glycols; C006903:carbopol 940; D008063:Thioctic Acid; D004317:Doxorubicin; D011094:Polyethyleneimine
keywords: Bioactive saccharide; Cell targeting; Drug delivery; Nanogel; Polyionic complex; Polypeptide; Reduction-responsive; pH-responsive