title: Boronic acid shell-crosslinked dextran-b-PLA micelles for acid-responsive drug delivery.
abstract: Herein, 3-carboxy-5-nitrophenylboronic acid (CNPBA) shell-crosslinked micelles based on amphiphilic dextran-block-polylactide (Dex-b-PLA) are prepared and used for efficient intracellular drug deliveries. Due to the reversible pH-dependent binding with diols to form boronate esters, CNPBA modified Dex-b-PLA shows excellent pH-sensitivity. In neutral aqueous conditions, CNPBA-Dex-b-PLA forms shell-crosslinked micelles to enable DOX loading, while in acid conditions, the boronate esters hydrolyze and the micelles de-crosslink to release loaded DOX. In vitro release studies indicate that the release of the DOX cargo is minimized at physiological conditions, while there is a burst release in response to low pHs. The cell viability of CNPBA-Dex-b-PLA investigated by MTT assay was more than 90%, indicating that, as a drug delivery system, CNPBA-Dex-b-PLA has good cytocompatibility. These features suggest that the pH-responsive biodegradable CNPBA-Dex-b-PLA can efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a favorable platform as a drug delivery system for cancer therapy.
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun, 130024, P. R. China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Chaoliang
authors.initials: C
authors.lastname: He
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D061986:MCF-7 Cells; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D001897:Boronic Acids; D003432:Cross-Linking Reagents; D003911:Dextrans; D008823:Micelles; D011091:Polyesters; D004317:Doxorubicin
keywords: dextran; drug carriers; micelles; pH-responsiveness; polylactide