Polyethylene glycol conjugated polymeric nanocapsules for targeted delivery of quercetin to folate-expressing cancer cells in vitro and in vivo

El-Gogary, Riham I., Rubio Carrero, Noelia, Wang, Julie Tzu-Wen, Al-Jamal, Wafa' T., Bourgognon, Maxime, Kafa, Houmam, Naeem, Muniba, Klippstein, Rebecca, Abbate, Vincenzo, Leroux, Frédéric, Bals, Sara, van Tendeloo, Gustaaf, Kamel, Amany O., Awad, Gehanne A. S., Mortada, Nahed D. and Al-Jamal, Khuloud T. (2014) Polyethylene glycol conjugated polymeric nanocapsules for targeted delivery of quercetin to folate-expressing cancer cells in vitro and in vivo. ACS Nano, 8 (2). 1384–1401. ISSN 1936-086X

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Abstract

In this work we describe the formulation and characterization of chemically modified polymeric nanocapsules incorporating the anticancer drug, quercetin, for the passive and active targeting to tumors. Folic acid was conjugated to poly (lactide-co-glycolide) (PLGA) polymer to facilitate active targeting to cancer cells. Two different methods for the conjugation of PLGA to folic acid were employed utilising polyethylene glycol (PEG) as a spacer. Characterisation of the conjugates was performed using FTIR and 1H-NMR studies. The PEG and Folic acid content was independent on the conjugation methodology employed. PEGylation has shown to reduce the size of the nanocapsule, moreover, Zeta potential was shown to be polymer-type dependent. Comparative studies on the cytotoxicity and cellular uptake of the different formulations by HeLa cells, in the presence and absence of excess folic acid, were carried out using MTT assay and Confocal Laser Scanning Microscopy, respectively. Both results confirmed the selective uptake and cytotoxicity of the folic acid targeted nanocapsules to the folate enriched cancer cells in a folate-dependent manner. Finally the passive tumor accumulation and the active targeting of the nanocapsules to folate-expressing cells were confirmed upon intravenous administration in HeLa or IGROV-1 tumor-bearing mice. The developed nanocapsules provide a system for targeted delivery of a range of hydrophobic anti-cancer drugs in vivo.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Pharmacy
UEA Research Groups:	Faculty of Science > Research Groups > Drug Delivery and Pharmaceutical Materials (former - to 2017)
Depositing User:	Pure Connector
Date Deposited:	21 Jan 2014 11:40
Last Modified:	24 Oct 2022 05:59
URI:	https://ueaeprints.uea.ac.uk/id/eprint/47268
DOI:	10.1021/nn405155b

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