Performing Department
Nutrition and Food Science
Non Technical Summary
Breast cancer (BC) is the most common type of cancer and a leading cause of cancer-related mortality among women in the United States. The development of an effective preventive strategy using dietary natural products with low toxicity and potential synergistic effects will significantly advance the area of BC prevention and treatment. Two important natural components including curcumin, a hydrophobic polyphenol derived from the rhizome of turmeric (Curcuma longa, an ancient herb), and genistein (GE), the most enriched isoflavone in soy, have shown profound beneficial effects against several human diseases including BC. However, major factors that dampen the clinical applications of these compounds in humans are due to the low pharmacokinetics and bioavailability as well as rapid metabolization through the system. Nanotechnology offers a robust solution to enhance the bioavailability and therapeutic efficacy of hydrophobic molecules like curcumin and GE. Therefore, the goal of this study is to develop novel encapsulation systems to effectively deliver both curcumin and GE in BC cells and increase their bioavailability and synergistic function in inhibition of BC. Successful implementation of this pilot study will provide novel nanotechnology-based approaches for the effective delivery of both curcumin and GE as promising natural remedies for BC treatment.
Animal Health Component
(N/A)
Research Effort Categories
Basic
70%
Applied
(N/A)
Developmental
30%
Goals / Objectives
The goal of this study is to develop a novel nanoencapsulation system to effectively deliver both curcumin and genistin (GE) in breast cancer (BC) cells and increase their bioavailability in inhibition of BC development. The specific objectives are:Objective 1. Develop two nanotechnology-based co-encapsulation systems for curcumin and GE.Objective 2. Evaluate the in vitro anticancer effects of the co-encapsulated curcumin and GE on BC cell lines.
Project Methods
Objective 1. Develop two nanotechnology-based co-encapsulation systems for curcumin and GE.We will develop nanoencapsulation systems for co-delivery of curcumin and GE using lipid-based or polymeric materials and compare their anticancer efficacy based on difference of charge density and material composition.Approach: We will: 1) fabricate nanoliposomes from lipid-based nanocarriers (i.e. phosphatidylcholine /Tween80) with small particle size (~80 nm) using thin-film evaporation method; 2) fabricate nanoparticles from oppositely charged nanocarriers (i.e. protein-based: zein with casein or cationic casein) with similar particle size (~120 nm) using pH-shift method; 3) characterize the nanoencapsulation systemsObjective 2. Evaluate the in vitro anticancer effects of the co-encapsulated curcumin and GE on BC cell lines.Approach: We will determine potential effects of co-encapsulated curcumin and GE on various BC cell lines including ER-positive BC (e.g., MCF-7, T47D, BT474), TNBC (MDA-MB-231, MDA-MB-157 and MDA-MB-468) including cell proliferation, migration/invasion, apoptosis and cell cycle. Cell proliferation will be assessed through MTT assays and colony-forming assays. Apoptosis and cell cycle analysis will be measured using flow cytometry. Cell migration/invasion will be determined by transwell cell migration assay and scratch wound healing assay to measure the treatment effects on cancer metastasis ability. We will also evaluate in vitro toxicology of co-encapsulated nanoparticles using normal human mammary epithelial cells (HMECs) and MCF10A cells. We will determine the potential additive or synergistic effects of this approach by comparing single-encapsulated curcumin or GE with the combination system. We will also test a series of key regulatory gene expression to determine potential mechanisms through which this approach exerts its anticancer effects.