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

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• 作者：Ankit K. Rochani ; Sivakumar Balasubramanian ; Aswathy Ravindran Girija ; Sreejith Raveendran ; Ankita Borah ; Yutaka Nagaoka ; Yoshikata Nakajima ; Toru Maekawa ; D. Sakthi Kumar ; ^{sakthi@toyo.jp" class="auth_mail" title="E-mail the corresponding author} ; ^{drsakthi@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nanotechnology ; Cancer chemotherapy ; Hsp90 inhibitor ; Nano formulation ; 17AAG
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：10 September 2016
• 年：2016
• 卷：511
• 期：1
• 页码：648-658
• 全文大小：2828 K

文摘

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.