Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo

Brian M. Barth, Rahul Sharma, Erhan I. Altinoǧlu, Thomas T. Morgan, Sriram S. Shanmugavelandy, James M. Kaiser, Christopher McGovern, Gail Matters, Jill P. Smith, Mark Kester, James Hansell Adair

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

The early diagnosis of cancer is the critical element in successful treatment and long-term favorable patient prognoses. The high rate of mortality is mainly attributed to the tendency for late diagnoses as symptoms may not occur until the disease has metastasized, as well as the lack of effective systemic therapies. Late diagnosis is often associated with the lack of timely sensitive imaging modalities. The promise of nanotechnology is presently limited by the inability to simultaneously seek, treat, and image cancerous lesions. This study describes the design and synthesis of fluorescent calcium phosphosilicate nanocomposite particles (CPNPs) that can be systemically targeted to breast and pancreatic cancer lesions. The CPNPs are a ∼20 nm diameter composite composed of an amorphous calcium phosphate matrix doped with silicate in which a near-infrared imaging agent, indocyanine green (ICG), is embedded. In the present studies, we describe and validate CPNP bioconjugation of human holotransferrin, anti-CD71 antibody, and short gastrin peptides via an avidin-biotin or a novel PEG-maleimide coupling strategy. The conjugation of biotinylated human holotransferrin (diferric transferrin) and biotinylated anti-CD71 antibody (anti-transferrin receptor antibody) to avidin-conjugated CPNPs (Avidin-CPNPs) permits targeting of transferrin receptors, which are highly expressed on breast cancer cells. Similarly, the conjugation of biotinylated pentagastrin to Avidin-CPNPs and decagastrin (gastrin-10) to PEG-CPNPs via PEG-maleimide coupling permits targeting of gastrin receptors, which are overexpressed in pancreatic cancer lesions. These bioconjugated CPNPs have the potential to perform as a theranostic modality, simultaneously enhancing drug delivery, targeting, and imaging of breast and pancreatic cancer tumors.

Original languageEnglish (US)
Pages (from-to)1279-1287
Number of pages9
JournalACS Nano
Volume4
Issue number3
DOIs
StatePublished - Mar 23 2010

Fingerprint

breast
calcium
Calcium
Nanocomposites
nanocomposites
cancer
Nanoparticles
nanoparticles
composite materials
Avidin
Composite materials
antibodies
Antibodies
lesions
Polyethylene glycols
Transferrin Receptors
Gastrins
conjugation
Cholecystokinin B Receptor
Imaging techniques

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Barth, Brian M. ; Sharma, Rahul ; Altinoǧlu, Erhan I. ; Morgan, Thomas T. ; Shanmugavelandy, Sriram S. ; Kaiser, James M. ; McGovern, Christopher ; Matters, Gail ; Smith, Jill P. ; Kester, Mark ; Adair, James Hansell. / Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo. In: ACS Nano. 2010 ; Vol. 4, No. 3. pp. 1279-1287.
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Barth, BM, Sharma, R, Altinoǧlu, EI, Morgan, TT, Shanmugavelandy, SS, Kaiser, JM, McGovern, C, Matters, G, Smith, JP, Kester, M & Adair, JH 2010, 'Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo', ACS Nano, vol. 4, no. 3, pp. 1279-1287. https://doi.org/10.1021/nn901297q

Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo. / Barth, Brian M.; Sharma, Rahul; Altinoǧlu, Erhan I.; Morgan, Thomas T.; Shanmugavelandy, Sriram S.; Kaiser, James M.; McGovern, Christopher; Matters, Gail; Smith, Jill P.; Kester, Mark; Adair, James Hansell.

In: ACS Nano, Vol. 4, No. 3, 23.03.2010, p. 1279-1287.

Research output: Contribution to journalArticle

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AU - Barth, Brian M.

AU - Sharma, Rahul

AU - Altinoǧlu, Erhan I.

AU - Morgan, Thomas T.

AU - Shanmugavelandy, Sriram S.

AU - Kaiser, James M.

AU - McGovern, Christopher

AU - Matters, Gail

AU - Smith, Jill P.

AU - Kester, Mark

AU - Adair, James Hansell

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