title: Low molecular-weight chitosan as a pH-sensitive stealth coating for tumor-specific drug delivery.
abstract: When a nanoparticle is developed for systemic application, its surface is typically protected by poly(ethylene glycol) (PEG) to help prolonged circulation and evasion of immune clearance. On the other hand, PEG can interfere with interactions between nanocarriers and target cells and negatively influence the therapeutic outcomes. To overcome this challenge, we propose low molecular-weight chitosan (LMWC) as an alternative surface coating, which can protect the nanomedicine in neutral pH but allow cellular interactions in the weakly acidic pH of tumors. LMWCs with a molecular weight of 2-4 kDa, 4-6.5 kDa, and 11-22 kDa were produced by hydrogen peroxide digestion and covalently conjugated with poly(lactic-co-glycolic acid) (PLGA). Nanoparticles created with PLGA-LMWC conjugates showed pH-sensitive cell interactions, which enabled specific drug delivery to cells in a weakly acidic environment. The hydrophilic LMWC layer reduced opsonization and phagocytic uptake. These properties qualify LMWCs as a promising biomaterial for pH-sensitive stealth coating.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Amoozgar
authors.forename: Joonyoung
authors.initials: J
authors.lastname: Park
authors.forename: Qingnuo
authors.initials: Q
authors.lastname: Lin
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D018613:Microscopy, Confocal; D015394:Molecular Structure; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D048271:Chitosan; D017239:Paclitaxel