title: Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo.
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 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.
authors.affiliation: Department of Materials Science and Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Barth
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Erhan I
authors.initials: EI
authors.lastname: Altinoğlu
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Morgan
authors.forename: Sriram S
authors.initials: SS
authors.lastname: Shanmugavelandy
authors.forename: James M
authors.initials: JM
authors.lastname: Kaiser
authors.forename: Christopher
authors.initials: C
authors.lastname: McGovern
authors.forename: Gail L
authors.initials: GL
authors.lastname: Matters
authors.forename: Jill P
authors.initials: JP
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Kester
authors.forename: James H
authors.initials: JH
authors.lastname: Adair
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D015195:Drug Design; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D043887:Receptor, Cholecystokinin B / Q000737:chemistry / Q000378:metabolism; D017640:Silicates / Q000737:chemistry*
chemical_list: D043887:Receptor, Cholecystokinin B; D017640:Silicates