Boronic Acid Shell-Crosslinked Dextran-b-PLA Micelles for Acid-Responsive Drug Delivery
Ziwei Zhao
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorXuemei Yao
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorZhe Zhang
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorCorresponding Author
Li Chen
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorChaoliang He
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 P. R. China
Search for more papers by this authorXuesi Chen
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 P. R. China
Search for more papers by this authorZiwei Zhao
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorXuemei Yao
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorZhe Zhang
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorCorresponding Author
Li Chen
Department of Chemistry, Northeast Normal University, Changchun, 130024 P. R. China
Search for more papers by this authorChaoliang He
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 P. R. China
Search for more papers by this authorXuesi Chen
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 P. R. China
Search for more papers by this authorAbstract
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.
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Figure S1.1H NMR spectrum of atactic PLA in CDCl3. Figure S2. 1H NMR spectra of dextran (a) and α-alkyne dextran (b) in DMSO-d6. Figure S3. FT-IR spectra of PDP-0 and PDP-3. Figure S4. UV-vis standard curve of CNPBA in DMSO. Figure S5. Plot of the emission intensity at 660 nm versus the log of concentration (mg mL−1) of PDP-0∼3 micelles at pH 7.4. Figure S6. Plot of the emission intensity at 660 nm versus the log of concentration (mg mL−1) of PDP-0 micelles at pH 5.5 and pH 7.4. Figure S7. Plot of the emission intensity at 660 nm versus the log of concentration (mg mL−1) of PDP-3 micelles at pH 5.5 and pH 7.4. |
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