Mild Hyperthermia Enhances Transport of Liposomal Gemcitabine and Improves In Vivo Therapeutic Response

Dickson K. Kirui, Christian Celia, Roberto Molinaro, Shyam S. Bansal, Donato Cosco, Massimo Fresta, Haifa Shen, Mauro Ferrari

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod-mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery, and antitumor efficacy in pancreatic cancer CAPAN-1 tumor model. MHT treatment leads to a threefold increase in accumulation of 80-nm liposomes and enhances spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment lead to a threefold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg kg-1 Gem Lip leads to a twofold increase in therapeutic efficacy and inhibition of CAPAN-1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect is confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg kg-1 Gem Lip achieves similar therapeutic efficacy as the use of 60 mg kg-1 free gemcitabine. In conclusion, improvements in vivo efficacy are demonstrated resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines.

Original languageEnglish (US)
Pages (from-to)1092-1103
Number of pages12
JournalAdvanced Healthcare Materials
Volume4
Issue number7
DOIs
StatePublished - May 1 2015

Keywords

  • Biological barriers
  • Cancer nanotherapeutics
  • Cancer therapy
  • Liposomal gemcitabine
  • Mild hyperthermia

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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