Enhance chemotherapy efficacy and minimize anticancer drug side effects by using reversibly pH- and redox-responsive cross-linked unimolecular micelles

Publication date: 5 May 2017
Source:Polymer, Volume 116
Author(s): Hamid Sadeghi Abandansari, Maryam Abuali, Mohammad Reza Nabid, Hassan Niknejad
Chemotherapy side effects elimination while keeping the original therapeutic advantages has been of extensive interest over last decades. We herein develope a new pH and redox-sensitive nanogel for glutathione-mediated intracellular drug delivery employing disulfide crosselinked unimolecular micelles. We developed H40-polycaprolactone-b-polyacrylic acid-b′-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate (i.e., H40-PCL-(b-PAA-b′-MPEG/PEG-FA)2) unimolecular micelles with targeting moieties on the periphery. It was then crosslinked with cystamine in order to generate a pH and redox-sensitive nanogel. Dynamic light scattering (DLS) was performed to study pH-dependent nanogel sizes. We applied Paclitaxel, a hydrophobic anticancer drug, into delivery system and examined triggered release behaviors at different pHs upon DTT buffer exposure. Our results demonstrated that DTT presence as reductive agent within acidic environment is essential for drug release. This may potentially reduce unwanted drug release at non-cancerous acidic tissues leading to eliminated side effects. We examined biocompatibility and cytotoxicity of free nanogel and PTX-loaded nanogel to normal and cancer HeLa cells using MTT assay. Nanogel HeLa cell uptake was confirmed by Fluorescein loading into the gel followed by fluorescent microscope imaging. Our novel strategy would have profound implications in both enhanced chemotherapy efficacy and minimized side effects.

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