title: Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation.
abstract: Heat Shock Protein 90 (Hsp90) has been extensively explored as a potential drug target for cancer therapies. 17- N-allylamino- 17-demethoxygeldanamycin (17AAG) was the first Hsp90 inhibitor to enter clinical trials for cancer therapy. However, native drug is being shown to have considerable anticancer efficacy against pancreatic cancer when used in combination therapy regime. Further, magnetic hyperthermia has shown to have promising effects against pancreatic cancer in combination with known cyto-toxic drugs under both target and non-targeted scenarios. Hence, in order to enhance the efficacy of 17AAG against pancreatic cancer, we developed poly (lactic-co-glycolic acid) (PLGA) coated, 17AAG and Fe3O4 loaded magnetic nanoparticle formulations by varying the relative concentration of polymer. We found that polymer concentration affects the magnetic strength and physicochemical properties of formulation. We were also able to see that our aqueous dispensable formulations were able to provide anti-pancreatic cancer activity for MIA PaCa-2 cell line in dose and time dependent manner in comparison to mice fibroblast cell lines (L929). Moreover, the in-vitro magnetic hyperthermia against MIA PaCa-2 provided proof principle that our 2-in-1 particles may work against cancer cell lines effectively.
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Ankit K
authors.initials: AK
authors.lastname: Rochani
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Aswathy
authors.initials: A
authors.lastname: Ravindran Girija
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Sreejith
authors.initials: S
authors.lastname: Raveendran
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Ankita
authors.initials: A
authors.lastname: Borah
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagaoka
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Yoshikata
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama 350-8585, Japan. Electronic address: sakthi@toyo.jp.
authors.forename: D Sakthi
authors.initials: DS
authors.lastname: Kumar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004339:Drug Compounding / Q000379:methods; D005290:Ferric Compounds / Q000008:administration & dosage / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011108:Polymers / Q000008:administration & dosage / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D005290:Ferric Compounds; D018841:HSP90 Heat-Shock Proteins; D011108:Polymers; C000499:ferric oxide
keywords: 17AAG; Cancer chemotherapy; Hsp90 inhibitor; Nano formulation; Nanotechnology