Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc) blocks tumor growth and metastases in preclinical models of pancreatic cancer

Savita Bisht, Masamichi Mizuma, Georg Feldmann, Niki A. Ottenhof, Seung Mo Hong, Dipankar Pramanik, Venugopal Chenna, Collins Karikari, Rajni Sharma, Michael S Goggins, Michelle Rudek-Renaut, Rajani Ravi, Amarnath Maitra, Anirban Maitra

Research output: Contribution to journalArticle

Abstract

Curcumin or diferuloylmethane is a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa). A large volume (several hundreds) of published reports has established the anticancer and chemopreventative properties of curcumin in preclinical models of every known major cancer type. Nevertheless, the clinical translation of curcumin has been significantly hampered due to its poor systemic bioavailability, which mandates that patients consume up to 8 to 10 g of the free drug orally each day to achieve detectable levels in circulation. We have engineered a polymeric nanoparticle encapsulated curcumin formulation (NanoCurc) that shows remarkably higher systemic bioavailability in plasma and tissues compared with free curcumin upon parenteral administration. In xenograft models of human pancreatic cancer established in athymic mice, administration of parenteral NanoCurc significantly inhibits primary tumor growth in both subcutaneous and orthotopic settings. The combination of parenteral NanoCurc with gemcitabine results in enhanced tumor growth inhibition versus either single agent, suggesting an additive therapeutic influence in vivo. Furthermore, this combination completely abrogates systemic metastases in orthotopic pancreatic cancer xenograft models. Tumor growth inhibition is accompanied by significant reduction in activation of nuclear factor-κB, as well as significant reduction in expression of matrix metalloproteinase-9 and cyclin D1, in xenografts treated with NanoCurc and gemcitabine. NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy.

Original languageEnglish (US)
Pages (from-to)2255-2264
Number of pages10
JournalMolecular Cancer Therapeutics
Volume9
Issue number8
DOIs
StatePublished - Aug 2010

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Curcumin
Pancreatic Neoplasms
Nanoparticles
Neoplasm Metastasis
Growth
Neoplasms
gemcitabine
Heterografts
Biological Availability
Curcuma
Rhizome
Cyclin D1
Matrix Metalloproteinase 9
Polyphenols
Nude Mice

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc) blocks tumor growth and metastases in preclinical models of pancreatic cancer. / Bisht, Savita; Mizuma, Masamichi; Feldmann, Georg; Ottenhof, Niki A.; Hong, Seung Mo; Pramanik, Dipankar; Chenna, Venugopal; Karikari, Collins; Sharma, Rajni; Goggins, Michael S; Rudek-Renaut, Michelle; Ravi, Rajani; Maitra, Amarnath; Maitra, Anirban.

In: Molecular Cancer Therapeutics, Vol. 9, No. 8, 08.2010, p. 2255-2264.

Research output: Contribution to journalArticle

Bisht, Savita ; Mizuma, Masamichi ; Feldmann, Georg ; Ottenhof, Niki A. ; Hong, Seung Mo ; Pramanik, Dipankar ; Chenna, Venugopal ; Karikari, Collins ; Sharma, Rajni ; Goggins, Michael S ; Rudek-Renaut, Michelle ; Ravi, Rajani ; Maitra, Amarnath ; Maitra, Anirban. / Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc) blocks tumor growth and metastases in preclinical models of pancreatic cancer. In: Molecular Cancer Therapeutics. 2010 ; Vol. 9, No. 8. pp. 2255-2264.
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AU - Hong, Seung Mo

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