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An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery

Najer, Adrian and Wu, Dalin and Nussbaumer, Martin G. and Schwertz, Geoffrey and Schwab, Anatol and Witschel, Matthias C. and Schafer, Anja and Diederich, Francois and Rottmann, Matthias and Palivan, Cornelia G. and Beck, Hans-Peter and Meier, Wolfgang. (2016) An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery. Nanoscale, 8. pp. 14858-14869.

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Official URL: http://edoc.unibas.ch/44258/

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Abstract

Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, and metabolic instability. Smart nanocarrier-based drug delivery systems provide means of solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol–disulfide exchange reaction between thiolated hydrophilic block and pyridyl disulfide functionalized hydrophobic block. These amphiphilic graft copolymers self-assembled into nanoparticles with mean diameters of about 30–50 nm and readily incorporated hydrophobic guest molecules. Fluorescence correlation spectroscopy (FCS) was used to study nanoparticle stability and triggered release of a model compound in detail. Long-term colloidal stability and model compound retention within the nanoparticles was found when analyzed in cell media at body temperature. In contrast, rapid, complete reduction-triggered disassembly and model compound release was achieved within a physiological reducing environment. The synthesized copolymers revealed no intrinsic cellular toxicity up to 1 mg mL−1. Drug-loaded reduction-sensitive nanoparticles delivered a hydrophobic model anticancer drug (doxorubicin, DOX) to cancer cells (HeLa cells) and an experimental, metabolically unstable antimalarial drug (the serine hydroxymethyltransferase (SHMT) inhibitor (±)-1) to Plasmodium falciparum-infected red blood cells (iRBCs), with higher efficacy compared to similar, non-sensitive drug-loaded nanoparticles. These responsive copolymer-based nanoparticles represent a promising candidate as smart nanocarrier platform for various drugs to be applied to different diseases, due to the biocompatibility and biodegradability of the hydrophobic block, and the protein-repellent hydrophilic block.
Faculties and Departments:05 Faculty of Science > Departement Chemie
05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)
UniBasel Contributors:Meier, Wolfgang P. and Beck, Hans-Peter and Rottmann, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:The Royal Society of Chemistry
ISSN:2040-3364
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Oct 2016 12:34
Deposited On:03 Oct 2016 12:34

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