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Dual disassembly and biological evaluation of enzyme/oxidation-responsive polyester-based nanoparticulates for tumor-targeting delivery


Dual disassembly and biological evaluation of enzyme/oxidation-responsive polyester-based nanoparticulates for tumor-targeting delivery

Hong, Sung Hwa, Larocque, Kevin, Jaunky, Dilan B., Piekny, Alisa J and Kwon Oh, Jung ORCID: https://orcid.org/0000-0002-4220-308X (2018) Dual disassembly and biological evaluation of enzyme/oxidation-responsive polyester-based nanoparticulates for tumor-targeting delivery. Colloids and Surfaces B: Biointerfaces . ISSN 09277765 (In Press)

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Official URL: http://dx.doi.org/10.1016/j.colsurfb.2018.09.013


Polyester-based nanoparticulates (NPs) are ideal nanocarriers for intracellular delivery of anticancer drugs because of their biocompatibility. However, an on-going challenge is the controlled and enhanced release of encapsulated therapeutics in response to unique changes that occur within cancer cells. Herein, we report the versatility of dual responses to enzymatic and oxidative reactions found in cancer cells toward the development of polyester-NPs as effective tumor-targeting intracellular nanocarriers. A facile nanoprecipitation method allows for the preparation of hydrophobic cores composed of novel polyester designed with esterase-responsive ester groups and oxidation-responsive sulfide linkages on their backbones, physically stabilized with poly(ethylene glycol)-based polymeric shells. The formed core/shell-type NPs with a diameter of 120 nm exhibit excellent colloidal stability in physiological conditions and in the presence of serum proteins. When exposed to esterase and hydrogen peroxide, NP integrity is disrupted, leading to the enhanced release of encapsulated doxorubicin, confirmed by dynamic light scattering and spectroscopic analysis. Combined results from epifluorescence microscopy, confocal laser scanning microscopy, flow cytometry, and cell viability demonstrate that doxorubicin-loaded NPs reveal rapid penetration and enhanced intracellular release of doxorubicin, thus inhibiting tumor progression. Importantly, the cellular uptake of doxorubicin-loaded core/shell NPs primarily via caveolae-dependent mechanism promotes their use in targeting a broad spectrum of cancers.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Article
Authors:Hong, Sung Hwa and Larocque, Kevin and Jaunky, Dilan B. and Piekny, Alisa J and Kwon Oh, Jung
Journal or Publication:Colloids and Surfaces B: Biointerfaces
Date:9 September 2018
  • Natural Science and Engineering Research Council (NSERC)
  • Discovery Grants
  • Canada Research Chair (CRC)
Digital Object Identifier (DOI):10.1016/j.colsurfb.2018.09.013
Keywords:ROS; esterase; dual stimuli-responsive degradation; polyester nanoparticles; controlled release; enhanced penetration; drug delivery
ID Code:984420
Deposited By: MONIQUE LANE
Deposited On:20 Sep 2018 20:30
Last Modified:20 Sep 2018 20:30


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