Inhibiting the Growth of Pancreatic Adenocarcinoma In Vitro and In Vivo through Targeted Treatment with Designer Gold Nanotherapeutics

Rachel A. Kudgus, Annamaria Szabolcs, Jameel Ahmad Khan, Chad A. Walden, Joel M Reid, J. David Robertson, Resham Bhattacharya, Priyabrata Mukherjee

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Pancreatic cancer is one of the deadliest of all human malignancies with limited options for therapy. Here, we report the development of an optimized targeted drug delivery system to inhibit advanced stage pancreatic tumor growth in an orthotopic mouse model. Method/Principal Findings: Targeting specificity in vitro was confirmed by preincubation of the pancreatic cancer cells with C225 as well as Nitrobenzylthioinosine (NBMPR - nucleoside transporter (NT) inhibitor). Upon nanoconjugation functional activity of gemcitabine was retained as tested using a thymidine incorporation assay. Significant stability of the nanoconjugates was maintained, with only 12% release of gemcitabine over a 24-hour period in mouse plasma. Finally, an in vivo study demonstrated the inhibition of tumor growth through targeted delivery of a low dose of gemcitabine in an orthotopic model of pancreatic cancer, mimicking an advanced stage of the disease. Conclusion: We demonstrated in this study that the gold nanoparticle-based therapeutic containing gemcitabine inhibited tumor growth in an advanced stage of the disease in an orthotopic model of pancreatic cancer. Future work would focus on understanding the pharmacokinetics and combining active targeting with passive targeting to further improve the therapeutic efficacy and increase survival.

Original languageEnglish (US)
Article numbere57522
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 6 2013

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gemcitabine
pancreatic neoplasms
adenocarcinoma
Pancreatic Neoplasms
Gold
gold
Adenocarcinoma
Tumors
Growth
therapeutics
neoplasms
Nanoconjugates
Neoplasms
Nucleoside Transport Proteins
drug delivery systems
Pharmacokinetics
disease models
nucleosides
Therapeutics
Drug Delivery Systems

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Inhibiting the Growth of Pancreatic Adenocarcinoma In Vitro and In Vivo through Targeted Treatment with Designer Gold Nanotherapeutics. / Kudgus, Rachel A.; Szabolcs, Annamaria; Khan, Jameel Ahmad; Walden, Chad A.; Reid, Joel M; Robertson, J. David; Bhattacharya, Resham; Mukherjee, Priyabrata.

In: PLoS One, Vol. 8, No. 3, e57522, 06.03.2013.

Research output: Contribution to journalArticle

Kudgus, Rachel A. ; Szabolcs, Annamaria ; Khan, Jameel Ahmad ; Walden, Chad A. ; Reid, Joel M ; Robertson, J. David ; Bhattacharya, Resham ; Mukherjee, Priyabrata. / Inhibiting the Growth of Pancreatic Adenocarcinoma In Vitro and In Vivo through Targeted Treatment with Designer Gold Nanotherapeutics. In: PLoS One. 2013 ; Vol. 8, No. 3.
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