Diels Alder-mediated release of gemcitabine from hybrid nanoparticles for enhanced pancreatic cancer therapy

Adeolu Oluwasanmi, Ayesha Manzur, Mohamed Abdelbasi, Rahan Elsini, Mohammed Albusai, Anthony Curtis, Clare Hoskins

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Hybrid nanoparticles (HNPs) have shown huge potential as drug delivery vehicles for pancreatic cancer. Currently, the first line treatment, gemcitabine, is only effective in 23.8% of patients. To improve this, a thermally activated system was developed by introducing a linker between HNPs and gemcitabine. Whereby, heat generation resulting from laser irradiation of the HNPs promoted linker breakdown resulting in prodrug liberation. In vitro evaluation in pancreatic adenocarcinoma cells, showed the prodrug was 4.3 times less cytotoxic than gemcitabine, but exhibited 11-fold improvement in cellular uptake. Heat activation of the formulation led to a 56% rise in cytotoxicity causing it to outperform gemcitabine by 26%. In vivo the formulation outperformed free gemcitabine with a 62% reduction in tumor weight in pancreatic xenografts. This HNP formulation is the first of its kind and has displayed superior anti-cancer activity as compared to the current first line drug gemcitabine after heat mediated controlled release.
Original languageEnglish
Pages (from-to)355-364
Number of pages10
JournalJournal of Controlled Release
Volume266
DOIs
Publication statusPublished - 22 Sep 2017

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Keywords

  • Diels Alder
  • thermo-responsive drug delivery
  • pancreatic cancer
  • hybrid nanoparticle
  • gemcitabine

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