Development of a New Nanocarrier for Dietary Garcinol: Characterization and In Vitro Efficacy Evaluation Using Breast Cancer Stem Cells Grown in Hypoxia. (10th February 2021)

• Record Type: Journal Article
• Authors: Hulangamuwa, Amal Charindra; Ediriweera, Meran Keshawa; Rajagopalan, Umapriyatharshini; Karunaratne, Desiree Nedra; Tennekoon, Kamani Hemamala; Samarakoon, Sameera Ranganath
• Other Names: Patarata Luis Academic Editor.
• Is Part Of: Journal of food quality. Volume 2021(2021)
• Publication Date: 2021-02-10
• Subjects: Food industry and trade -- Quality control -- Periodicals; Food industry and trade -- Standards -- Periodicals; Food -- Periodicals; 664.07
• DOI: 10.1155/2021/6654211
• Languages: English
• ISSNs: 0146-9428

Abstract

Abstract : Garcinol (GA), a polyisoprenylated benzophenone derivative, is one of the major phytochemicals found in a number of fruits of Garcinia . This study aimed to develop a new nanodelivery system comprising GA, hyaluronic acid (HA), and poly(lactic-co-glycolic acid) (PLGA) to actively target breast cancer stem cells (bCSCs) grown under hypoxic conditions. HA has been reported to show higher affinity for the cluster-determinant 44 receptor (CD44), while PLGA is an FDA-approved biodegradable polymer used in clinical applications. Nanoparticles (NPs) were prepared by emulsion solvent diffusion technique using DMAB as the emulsifier. Following preparation, particle size, surface charge, and polydispersity index of NPs were characterized. Antiproliferative effects of NPs were assessed by the WST-1 cell proliferation assay. Apoptotic effects of NPs were evaluated by the caspase-3/7 assay. Effects of prepared NPs on the expression of genes related to hypoxia-inducing factors ( HIF- 1 α and HIF- 2 α ) and notch ligands ( DLL 1 and Jagged 1) were evaluated using real-time PCR. HA-coated garcinol-loaded NPs (HA-GA-NPs) showed greater antiproliferative effects in bCSCs grown under hypoxia. Moreover, HA-GA-NPs showed an improved cellular uptake via receptor-mediated endocytosis compared to non-HA-coated GA-NPs. Exposure to GA-HA-NPs resulted in a significant downregulation in hypoxia-inducing factors and notch pathway-related genes. Activation of caspase-3/7 confirmed the HA-GA-NPs can induce apoptosis in bCSCs. Overall findings of the study confirm that HA-GA-NPs can be considered as an effective nanodelivery system to target bCSCs grown under the hypoxic microenvironment.