title: Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells.
abstract: This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR-) cells. The expression of a prominent anticancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer.
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Kislay
authors.initials: K
authors.lastname: Roy
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Yogesh S
authors.initials: YS
authors.lastname: Patel
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Kanwar
authors.affiliation: Institute for Frontier Materials (IFM), Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Rangam
authors.initials: R
authors.lastname: Rajkhowa
authors.affiliation: Institute for Frontier Materials (IFM), Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Xungai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Jagat R
authors.initials: JR
authors.lastname: Kanwar
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006801:Humans; D007501:Iron / Q000737:chemistry; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology*; D061986:MCF-7 Cells / Q000187:drug effects; D051379:Mice; D009036:Moths / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D047011:Silk / Q000737:chemistry*
chemical_list: D001059:Apoproteins; D011956:Receptors, Cell Surface; D047011:Silk; C039223:apolactoferrin; C038340:lactoferrin receptors; D048271:Chitosan; D007501:Iron; D007781:Lactoferrin
keywords: apoptosis; bovine lactoferrin; breast cancer; epidermal growth factor receptor; silk nanoparticles