Intracellular fate of a targeted delivery system

Chitta Ranjan Patra, Sheng Cao, Stephanie Safgren, Resham Bhattacharya, Matthew M. Ames, Vijay Shah, Joel M. Reid, Priyabrata Mukherjee

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Targeted delivery of a drug to the malignant cells should result in enhanced therapeutic efficacy with low to minimal side effects. This is a widely accepted concept, but limited in application due to lack of available technologies and process of validation. Therefore, fabrication of a "smart" targeted delivery system with a tunable release profile of drug in a particular cellular compartment constitutes an essential component in targeted delivery. Nanotechnology can play an important role in this aspect. In this article, we report the investigation on the intracellular fate of such a targeted delivery system containing gold nanoparticle (AuNP) as a delivery vehicle, gemcitabine (Gem) as a cytotoxic drug and cetuximab (C225) as a targeting agent. To confirm the intracellular uptake of the nanoconjugates, we determined the intracellular gemcitabine triphosphate (GemTP) concentration of AsPC-1 cells under targeted and non-targeted condition. Furthermore, we have performed transmission electron microscopic (TEM) analysis of AsPC-1 cells (a pancreatic cancer cell line with a high degree of EGFR expression) after treatment with Au-C225-Gem and its non-targeted counterpart Au-lgG-Gem to confirm the intracellular uptake and determine the intracellular localizations of the nanoconjugates. Stability of Au-C225-Gem is studied in terms of the release of C225 and Gem under different settings such as in the cell growth media, in mouse plasma, under intracellular GSH concentration and finally in endosomal acidic environment. Results obtained from all of the experiments described above suggest that the nanoconjugate is significantly stable outside the cell both under in vitro and in vivo setting. However, the nanconjugate dissociates under intracellular environment at high GSH concentration and at acidic endosomal pH releasing functionally active Gem. These studies will have significant impact, on rationally designing a nanoconjugate for a successful targeted delivery.

Original languageEnglish (US)
Pages (from-to)508-514
Number of pages7
JournalJournal of Biomedical Nanotechnology
Volume4
Issue number4
DOIs
StatePublished - Dec 1 2008

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Keywords

  • Drug delivery
  • EGFR
  • Fate
  • Gold nanoparticle
  • Targeting

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Cite this

Patra, C. R., Cao, S., Safgren, S., Bhattacharya, R., Ames, M. M., Shah, V., Reid, J. M., & Mukherjee, P. (2008). Intracellular fate of a targeted delivery system. Journal of Biomedical Nanotechnology, 4(4), 508-514. https://doi.org/10.1166/jbn.2008.016