Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers.

Abstract

The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1(+)/CIMP2(-)/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER(-)/PR(-)/HER2(-); MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm(3), and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm(3). In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm(3) within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy.

• Authors: Sishir K Kamalapuram, Rupinder K Kanwar, Kislay Roy, Rajneesh Chaudhary, Rakesh Sehgal, Jagat R Kanwar
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 11 Pg. 1349-66 ( 2016) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 27099495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Ferric Compounds
• Nanocapsules
• zinc-binding protein
• ferric oxide
• Lactoferrin
• Zinc

Topics

• Adenocarcinoma (drug therapy)
• Animals
• Carrier Proteins (metabolism)
• Cattle
• Colonic Neoplasms (drug therapy)
• Female
• Ferric Compounds (chemistry)
• Humans
• Lactoferrin (chemistry)
• Mice
• Mice, Nude
• Nanocapsules (administration & dosage, chemistry)
• Theranostic Nanomedicine
• Triple Negative Breast Neoplasms (drug therapy)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Zinc (chemistry)