title: Target specific delivery of anticancer drug in silk fibroin based 3D distribution model of bone-breast cancer cells.
abstract: To avoid the indiscriminating action of anticancer drugs, the cancer cell specific targeting of drug molecule becomes a preferred choice for the treatment. The successful screening of the drug molecules in 2D culture system requires further validation. The failure of target specific drug in animal model raises the issue of creating a platform in between the in vitro (2D) and in vivo animal testing. The metastatic breast cancer cells migrate and settle at different sites such as bone tissue. This work evaluates the in vitro 3D model of the breast cancer and bone cells to understand the cellular interactions in the presence of a targeted anticancer drug delivery system. The silk fibroin based cytocompatible 3D scaffold is used as in vitro 3D distribution model. Human breast adenocarcinoma and osteoblast like cells are cocultured to evaluate the efficiency of doxorubicin loaded folic acid conjugated silk fibroin nanoparticle as drug delivery system. Decreasing population of the cancer cells, which lower the levels of vascular endothelial growth factors, glucose consumption, and lactate production are observed in the drug treated coculture constructs. The drug treated constructs do not show any major impact on bone mineralization. The diminished expression of osteogenic markers such as osteocalcein and alkaline phosphatase are recorded. The result indicates that this type of silk based 3D in vitro coculture model may be utilized as a bridge between the traditional 2D and animal model system to evaluate the new drug molecule (s) or to reassay the known drug molecules or to develop target specific drug in cancer research.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur , Kharagpur, West Bengal 721302, India.
authors.forename: Bano
authors.initials: B
authors.lastname: Subia
authors.forename: Tuli
authors.initials: T
authors.lastname: Dey
authors.forename: Shaily
authors.initials: S
authors.lastname: Sharma
authors.forename: Subhas C
authors.initials: SC
authors.lastname: Kundu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D012831:Bombyx; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005260:Female; D005349:Fibroins / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D009362:Neoplasm Metastasis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D005349:Fibroins
keywords: 3D in vitro model; bone metastasis; coculture; drug delivery; silk fibroin