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

Ankit K. Rochani, Sivakumar Balasubramanian, Aswathy Ravindran Girija, Sreejith Raveendran, Ankita Borah, Yutaka Nagaoka, Yoshikata Nakajima, Toru Maekawa, D. Sakthi Kumar

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)648-658
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume511
Issue number1
DOIs
Publication statusPublished - 10 Sep 2016

Fingerprint

tanespimycin
HSP90 Heat-Shock Proteins
Pancreatic Neoplasms
Cell Line
Neoplasms
Polymers
Fever
Pharmaceutical Preparations
Poisons
Therapeutics
Nanoparticles
Fibroblasts
Clinical Trials

Keywords

  • 17AAG
  • Cancer chemotherapy
  • Hsp90 inhibitor
  • Nano formulation
  • Nanotechnology

Cite this

Rochani, A. K., Balasubramanian, S., Ravindran Girija, A., Raveendran, S., Borah, A., Nagaoka, Y., ... Kumar, D. S. (2016). Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation. International Journal of Pharmaceutics, 511(1), 648-658. https://doi.org/10.1016/j.ijpharm.2016.07.048
Rochani, Ankit K. ; Balasubramanian, Sivakumar ; Ravindran Girija, Aswathy ; Raveendran, Sreejith ; Borah, Ankita ; Nagaoka, Yutaka ; Nakajima, Yoshikata ; Maekawa, Toru ; Kumar, D. Sakthi. / Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation. In: International Journal of Pharmaceutics. 2016 ; Vol. 511, No. 1. pp. 648-658.
@article{442b9a47c0f740e7a83397f980a74707,
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.",
keywords = "17AAG, Cancer chemotherapy, Hsp90 inhibitor, Nano formulation, Nanotechnology",
author = "Rochani, {Ankit K.} and Sivakumar Balasubramanian and {Ravindran Girija}, Aswathy and Sreejith Raveendran and Ankita Borah and Yutaka Nagaoka and Yoshikata Nakajima and Toru Maekawa and Kumar, {D. Sakthi}",
year = "2016",
month = "9",
day = "10",
doi = "10.1016/j.ijpharm.2016.07.048",
language = "English",
volume = "511",
pages = "648--658",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
number = "1",

}

Rochani, AK, Balasubramanian, S, Ravindran Girija, A, Raveendran, S, Borah, A, Nagaoka, Y, Nakajima, Y, Maekawa, T & Kumar, DS 2016, 'Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation', International Journal of Pharmaceutics, vol. 511, no. 1, pp. 648-658. https://doi.org/10.1016/j.ijpharm.2016.07.048

Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation. / Rochani, Ankit K.; Balasubramanian, Sivakumar; Ravindran Girija, Aswathy; Raveendran, Sreejith; Borah, Ankita; Nagaoka, Yutaka; Nakajima, Yoshikata; Maekawa, Toru; Kumar, D. Sakthi.

In: International Journal of Pharmaceutics, Vol. 511, No. 1, 10.09.2016, p. 648-658.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation

AU - Rochani, Ankit K.

AU - Balasubramanian, Sivakumar

AU - Ravindran Girija, Aswathy

AU - Raveendran, Sreejith

AU - Borah, Ankita

AU - Nagaoka, Yutaka

AU - Nakajima, Yoshikata

AU - Maekawa, Toru

AU - Kumar, D. Sakthi

PY - 2016/9/10

Y1 - 2016/9/10

N2 - 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.

AB - 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.

KW - 17AAG

KW - Cancer chemotherapy

KW - Hsp90 inhibitor

KW - Nano formulation

KW - Nanotechnology

UR - http://www.scopus.com/inward/record.url?scp=84979743286&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2016.07.048

DO - 10.1016/j.ijpharm.2016.07.048

M3 - Article

C2 - 27469073

AN - SCOPUS:84979743286

VL - 511

SP - 648

EP - 658

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1

ER -