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Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

Mahidhara, Ganesh, Kanwar, Rupinder K., Roy, Kislay and Kanwar, Jagat R . 2015, Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism, International journal of nanomedicine, vol. 10, pp. 4081-4098, doi: 10.2147/IJN.S75877.

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Title Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism
Author(s) Mahidhara, Ganesh
Kanwar, Rupinder K.
Roy, Kislay
Kanwar, Jagat R .ORCID iD for Kanwar, Jagat R . orcid.org/0000-0003-3728-9568
Journal name International journal of nanomedicine
Volume number 10
Start page 4081
End page 4098
Total pages 18
Publisher Dove Medical Press
Place of publication Auckland, N. Z.
Publication date 2015
ISSN 1178-2013
Keyword(s) Fe-bLf
breast cancer
miRNA
oral delivery
xenograft
Science & Technology
Life Sciences & Biomedicine
Nanoscience & Nanotechnology
Pharmacology & Pharmacy
Science & Technology - Other Topics
IMMUNOGENE THERAPY
CHITOSAN
NANOPARTICLES
CHEMOTHERAPY
DELIVERY
ANEMIA
DOXORUBICIN
PACLITAXEL
MANAGEMENT
APOPTOSIS
Summary We determined the anticancer efficacy and internalization mechanism of our polymeric-ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts.
Language eng
DOI 10.2147/IJN.S75877
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, Dove Medical Press
Free to Read? Yes
Use Rights Creative Commons Attribution non-commercial licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30074625

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.