Journal
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
Volume 50, Issue 1, Pages 228-239Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/21691401.2022.2118758
Keywords
Genistein; ovarian cancer; folate receptor targeting; PLGA; cellular internalization
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Funding
- University Grants Commission, New Delhi, India [5-63/2016[IC]]
- King Saud University, Riyadh, Saudi Arabia [RSP2021/301]
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In this study, folate receptor-targeted and PEGylated poly(lactide-co-glycolide) nanoparticles containing GEN were successfully developed for targeted delivery to ovarian cancer cells. These nanoparticles showed improved water solubility, sustained release of GEN, and increased cellular uptake in folate receptor-overexpressing ovarian cancer cells. The GEN-containing nanoparticles exhibited superior anticancer activity compared to non-targeted nanoparticles.
Genistein (GEN), a natural isoflavone possesses a wide range of pharmacological properties and nutraceutical applications. GEN has been studied for its anticancer activity against different types of cancers, but its use in clinical practice is limited due to its low water solubility, rapid metabolism and excretion, lack of cancer cell targeting and poor bioavailability. In the present study, we investigated folate receptor-targeted and PEGylated poly(lactide-co-glycolide) nanoparticles (PLGA-PEG-FA NPs) containing GEN for targeted delivery to ovarian cancer cells. PLGA-PEG and PLGA-PEG-FA polymer conjugates were synthesized and characterized. Nano-precipitation method was employed for the fabrication of NPs of PLGA, PLGA-PEG and PLGA-PEG-FA containing GEN. GEN containing PLGA-PEG and PLGA-PEG-FA NPs prepared were small (104.17 +/- 1.61 and 125.41 +/- 3.11 nm, respectively) and exhibited sustained release of GEN for around six days. Folate-decorated PLGA-PEG NPs showed increased cellular uptake in comparison to non-targeted PLGA-PEG NPs. The GEN containing PLGA-PEG-FA NPs showed superior anticancer activity than non-targeted PLGA and PLGA-PEG NPs in folate receptor-overexpressing ovarian cancer cell line, SKOV-3. The IC50 of GEN, GEN encapsulated NPs of PLGA, PLGA-PEG and PLGA-PEG-FA were 51.48, 26.70, 23.43 and 11.98 mu g/ml, respectively. Folate-targeted PLGA nanoparticles could be developed for potential target-specific delivery of GEN in the treatment of ovarian cancer.
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