title: Solubility enhancement and targeted delivery of a potent anticancer flavonoid analogue to cancer cells using ligand decorated dendrimer nano-architectures.
abstract: Conventional chemotherapy using small molecule drugs is marred by several challenges such as short half-life, low therapeutic index and adverse systemic side effects. In this regard, targeted therapies using ligand directed polyamidoamine (PAMAM) dendrimers could be a promising strategy to specifically deliver anticancer drugs to cancer cells overexpressing complementary receptor binding domains. The aim of this study was to utilize folate decorated PAMAM to enhance the aqueous solubility of a highly hydrophobic but very potent anticancer flavonoid analogue, 3,4-difluorobenzylidene diferuloylmethane (CDF) and to deliver it specifically to folate receptor overexpressing cervical cancer cells (HeLa) and ovarian cancer cells (SKOV3). As compared to the non-targeted formulation, the targeted formulation exhibited significant anticancer activity with higher accumulation in folate receptor overexpressing cells, larger population of apoptotic cancer cells, elevated expression of tumor suppressor phosphatase and tensin homolog (PTEN), and inhibition of nuclear factor kappa B (NFκB) which further confirmed the targeting ability and the promising anticancer activity of the folate based nanoformulation.
authors: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
authors: Duy
authors: D
authors: Luong
authors: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
authors: Prashant
authors: P
authors: Kesharwani
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
authors: Bryan A
authors: BA
authors: Killinger
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
authors: Anna
authors: A
authors: Moszczynska
authors: Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
authors: Fazlul H
authors: FH
authors: Sarkar
authors: Interdisciplinary Science & Technology Research Academy, Department of Chemistry, Abeda Inamdar College, Azam Campus, University of Pune, Pune 411001, India.
authors: Subhash
authors: S
authors: Padhye
authors: John D. Dingell VA Medical Center, Wayne State University, Detroit, MI 48201, USA; Department of Oncology, Wayne State University, Detroit, MI 48201, USA; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
authors: Arun K
authors: AK
authors: Rishi
authors: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA. Electronic address: arun.iyer@wayne.edu.
authors: Arun K
authors: AK
authors: Iyer
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry*; D036381:Diarylheptanoids; D004337:Drug Carriers / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D012995:Solubility
chemical_list: C000611228:3,4-difluorobenzylidenecurcumin; D000972:Antineoplastic Agents, Phytogenic; D050091:Dendrimers; D036381:Diarylheptanoids; D004337:Drug Carriers; D005419:Flavonoids; D058975:Folate Receptor 1; D016328:NF-kappa B; C104700:PAMAM Starburst; D005492:Folic Acid; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D003474:Curcumin
keywords: 34-Difluorobenzylidene diferuloylmethane (CDF); Cervical cancer; Flavonoid analogue; Folate receptor targeting; Ovarian cancer; PAMAM dendrimer; Targeted drug delivery