期刊
JOURNAL OF FOOD QUALITY
卷 2021, 期 -, 页码 -出版社
WILEY-HINDAWI
DOI: 10.1155/2021/6654211
关键词
-
资金
- Institute of Biochemistry, Molecular Biology and Biotechnology (IBMBB), University of Colombo
- National Research Council [NRC-14-067]
- National Science Foundation of Sri Lanka [NSF/RPHS/2016/C-07]
The study developed a new nanodelivery system comprising of garcinol, hyaluronic acid (HA), and poly(lactic-co-glycolic acid) (PLGA) to target breast cancer stem cells (bCSCs) grown under hypoxic conditions. The HA-coated garcinol-loaded NPs (HA-GA-NPs) showed enhanced antiproliferative effects in bCSCs and improved cellular uptake via receptor-mediated endocytosis, leading to apoptosis. Overall, the findings suggest that HA-GA-NPs can effectively target bCSCs in the hypoxic microenvironment.
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 alpha and HIF-2 alpha) and notch ligands (DLL1 and Jagged1) 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据