Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers.
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.
Nanomedicine Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular and Medical Research, Faculty of Health, Deakin University, Geelong, VIC, Australia.
Sishir K
SK
Kamalapuram
Nanomedicine Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular and Medical Research, Faculty of Health, Deakin University, Geelong, VIC, Australia.
Rupinder K
RK
Kanwar
Nanomedicine Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular and Medical Research, Faculty of Health, Deakin University, Geelong, VIC, Australia.
Kislay
K
Roy
Nanomedicine Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular and Medical Research, Faculty of Health, Deakin University, Geelong, VIC, Australia.
Rajneesh
R
Chaudhary
Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Rakesh
R
Sehgal
Nanomedicine Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular and Medical Research, Faculty of Health, Deakin University, Geelong, VIC, Australia.
Jagat R
JR
Kanwar
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D000068936:Theranostic Nanomedicine; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D015032:Zinc / Q000737:chemistry*
D002352:Carrier Proteins; D005290:Ferric Compounds; D053769:Nanocapsules; C017800:zinc-binding protein; C000499:ferric oxide; D007781:Lactoferrin; D015032:Zinc
multimodular cancer therapy; nanocapsules; nanomedicine; real-time imaging; theranostic