Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation

• Published in: International journal of pharmaceutics Vol. 511; no. 1; pp. 648 - 658
• Main Authors: Rochani, Ankit K., Balasubramanian, Sivakumar, Ravindran Girija, Aswathy, Raveendran, Sreejith, Borah, Ankita, Nagaoka, Yutaka, Nakajima, Yoshikata, Maekawa, Toru, Kumar, D. Sakthi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-09-2016
• Subjects: 17AAG; Animals; Cancer chemotherapy; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Drug Compounding - methods; Ferric Compounds - administration & dosage; Ferric Compounds - metabolism; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - chemistry; HSP90 Heat-Shock Proteins - metabolism; Hsp90 inhibitor; Humans; Mice; Nano formulation; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Nanotechnology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Polymers - administration & dosage; Polymers - metabolism; Protein Structure, Secondary; Cancer chemotherapy; Hsp90 inhibitor; 17AAG; Nano formulation; Nanotechnology
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.07.048

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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.