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 approximately 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.