title: Polyvalent Folate-Dendrimer-Coated Iron Oxide Theranostic Nanoparticles for Simultaneous Magnetic Resonance Imaging and Precise Cancer Cell Targeting.
abstract: The low therapeutic index of conventional chemotherapy and poor prognosis of patients diagnosed with metastatic cancers are prompting clinicians to adopt newer strategies to simultaneously detect cancer lesions at an early stage and to precisely deliver anticancer drugs to tumor sites. In this study, we employed a novel strategy to engineer a polyvalent theranostic nanocarrier consisting of superparamagnetic iron oxide nanoparticle core (SPIONs) decorated with folic acid-polyamidoamine dendrimers surface (FA-PAMAM). In addition, a highly potent hydrophobic anticancer agent 3,4-difluorobenzylidene-curcumin (CDF) was coloaded in the FA-PAMAM dendrimer to increase its solubility and assess its therapeutic potentials. The resulting targeted nanoparticles (SPIONs@FA-PAMAM-CDF) exhibited high MR contrast. When tested on folate receptor overexpressing ovarian (SKOV3) and cervical (HeLa) cancer cells, the CDF loaded targeted nanoformulations showed higher accumulation with a better anticancer activity as compared to the nontargeted counterparts, possibly due to multivalent folate receptor binding interaction with cells overexpressing the target. The results were corroborated by observation of a larger population of cells undergoing apoptosis due to upregulation of tumor suppressor phosphatase and tensis homologue (PTEN), caspase 3, and inhibition of NF-κB in groups treated with the targeted formulations, which further confirmed the ability of the multivalent theranostic nanoparticles for simultaneous imaging and therapy of cancers.
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , 259 Mack Avenue, Detroit, Michigan 48201, United States.
authors.forename: Duy
authors.initials: D
authors.lastname: Luong
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , 259 Mack Avenue, Detroit, Michigan 48201, United States.
authors.forename: Samaresh
authors.initials: S
authors.lastname: Sau
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , 259 Mack Avenue, Detroit, Michigan 48201, United States.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kesharwani
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , 259 Mack Avenue, Detroit, Michigan 48201, United States.|Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, Michigan 48201, United States.
authors.forename: Arun K
authors.identifier: 0000-0002-4428-0222
authors.initials: AK
authors.lastname: Iyer
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry; D036381:Diarylheptanoids; D016503:Drug Delivery Systems; D005290:Ferric Compounds / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry; D000068936:Theranostic Nanomedicine / Q000379:methods*; D015854:Up-Regulation
chemical_list: C000611228:3,4-difluorobenzylidenecurcumin; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D050091:Dendrimers; D036381:Diarylheptanoids; D005290:Ferric Compounds; D016328:NF-kappa B; C104700:PAMAM Starburst; C531249:Poly(amidoamine); D011073:Polyamines; C000499:ferric oxide; D005492:Folic Acid; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D003474:Curcumin