Mitochondriotropic Nanoemulsified Genistein-Loaded Vehicles for Cancer Therapy

Part of the Methods in Molecular Biology book series (MIMB, volume 1265)

Abstract

Genistein (Gen), a major soy isoflavone, produces extensive pro-apoptotic anticancer effects, mediated predominantly via induction of mitochondrial damage. Based on several biophysical model criteria, our rational assumptions for the native mitochondrial selectivity of Gen allowed its design as a cationic lipid-based nanocarrier (NC) system. Proof-of-concept nano-formulations, lipidic micelles (Mic), and nanoemulsions (NEs) incorporated Gen, which serves as therapeutic and targeting moieties, specific for mitochondria. Our in vitro experimental data demonstrated superior physicochemical properties and significant cytotoxicity of Gen-NCs (five- to tenfolds lower EC50) compared to all drug controls, in hepatic and colon carcinomas. The established mitochondria-specific accumulation of the various Gen-NCs positively correlated with marked mitochondrial depolarization effects. Within first 24 h, Gen-NC treatments ultimately lead to distinct activation of intrinsic apoptotic pathway markers, such as cytosolic cytochrome c and specific caspase-9 vs. nonspecific caspases-3, 7, and 8. Such mechanistic evidence of the mitochondriotropic activity of our Gen-NC platforms favors their prospective as intracellularly targeted delivery nano-vehicles, to enhance anticancer efficacy of different co-formulated chemotherapeutic agents.

Key words

Isoflavone Mitochondrial damage Mitochondriotropic Genistein Caspase enzymes Cytochrome c Apoptosis 

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jimmy Pham
    • 1
  • Oliver Grundmann
    • 2
    • 3
  • Tamer Elbayoumi
    • 3
    • 4
  1. 1.Arizona College of Osteopathic MedicineMidwestern UniversityGlendaleUSA
  2. 2.Department of Medicinal Chemistry, College of PharmacyUniversity of FloridaGainesvilleUSA
  3. 3.Department of Pharmaceutical Sciences, College of Pharmacy-GlendaleMidwestern UniversityGlendaleUSA
  4. 4.Department of Pharmaceutical Sciences, College of Pharmacy-GlendaleMidwestern UniversityGlendaleUSA

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