title: Milk derived colloid as a novel drug delivery carrier for breast cancer.
abstract: Triple negative breast cancer has an extremely poor prognosis when chemotherapy is no longer effective. To overcome drug resistance, novel drug delivery systems based on nanoparticles have had remarkable success. We produced a novel nanoparticle component 'MDC' from milk-derived colloid. In order to evaluate the anti-cancer effect of MDC, we conducted in vitro and in vivo experiments on cancer cell lines and a primary tumor derived breast xenograft. Doxorubicin (Dox) conjugated to MDC (MDC-Dox) showed higher cancer cell growth inhibition than MDC alone especially in cell lines with high EGFR expression. In a mouse melanoma model, MDC-Dox significantly suppressed tumor growth when compared with free Dox. Moreover, in a primary tumor derived breast xenograft, one of the mice treated with MDC-Dox showed partial regression, while mice treated with free Dox failed to show any suppression of tumor growth. We have shown that a novel nanoparticle compound made of simple milk-derived colloid has the capability for drug conjugation, and serves as a tumor-specific carrier of anti-cancer drugs. Further research on its safety and ability to carry various anti-cancer drugs into multiple drug-resistant primary breast models is warranted.
authors.affiliation: a Department of Otolaryngology-Head and Neck Surgery ; Johns Hopkins School of Medicine ; Baltimore , MD USA.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayashi
authors.forename: Nissim
authors.initials: N
authors.lastname: Silanikove
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chang
authors.forename: Rajani
authors.initials: R
authors.lastname: Ravi
authors.forename: Vui
authors.initials: V
authors.lastname: Pham
authors.forename: Gilson
authors.initials: G
authors.lastname: Baia
authors.forename: Keren
authors.initials: K
authors.lastname: Paz
authors.forename: Mariana
authors.initials: M
authors.lastname: Brait
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor / Q000187:drug effects; D003102:Colloids / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D008810:Mice, Inbred C57BL; D008892:Milk / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003102:Colloids; D004337:Drug Carriers; D004317:Doxorubicin
keywords: Dox, doxorubicin; Doxil; EGFR, epidermal growth factor receptor; EPR, enhanced permeability and retention; FITC, Fluorescein isothiocyanate; MDC, milk-derived colloid; MDC-Dox, Dox conjugated to MDC; MDR, multi-drug resistance; MDSC, myeloid-derived suppressor cells; NBC, triple-negative breast cancer; Pgp, P-glycoprotein, PL-Dox, pegylated lipopsomal doxorubicine; T PLD, pegylated liposomal doxorubicine; breast cancer; doxorubicin; milk; nanoparticle; xenograft