title: Killed Bacillus subtilis spores expressing streptavidin: a novel carrier of drugs to target cancer cells.
abstract: Carriers of drugs in cancer therapy are required to reduce side-effects of the drugs to normal cells. Here we constructed killed recombinant Bacillus subtilis spores (SA1) that expressed streptavidin as a chimeric fusion to the spore coat protein CotB and used the spores as bioparticle carrier. When bound with biotinylated cetuximab these spores could specifically target to the epidermal growth factor receptor on HT 29 colon cancer cells, thereby delivered paclitaxel to the cells with 4-fold higher efficiency, as indicated by fluorescent intensity of paclitaxel Oregon Green 488 bound to HT29 cells. Based on real-time monitoring of cell index, the IC50 of growth of HT29 cells by paclitaxel-SA1-cetuximab was estimated to be 2.9 nM approximately 5-fold lower than water-soluble paclitaxel (14.5 nM). Instability of DNA content was observed when cells were treated with 16 nM paclitaxel-SA1-cetuximab, resulting in a 2-fold enhancement in polyploidy cells. Thus, by targeting the release of paclitaxel to HT29 cells, spore-associated cetuximab augmented the inhibitory effect of paclitaxel on cell division and proliferation. The SA1 could be used as a "universal" drug carrier to target specific biomarkers on cancer cells by conjugating with suitable biotinylated antibodies.
authors.affiliation: Key laboratory of Enzyme and Protein Technology, VNU University of Science, Hanoi, Vietnam.
authors.forename: Van Anh Thi
authors.initials: VA
authors.lastname: Nguyen
authors.forename: Hong Anh
authors.initials: HA
authors.lastname: Huynh
authors.forename: Tong Van
authors.initials: TV
authors.lastname: Hoang
authors.forename: Ngoc Thi
authors.initials: NT
authors.lastname: Ninh
authors.forename: An Thi Hong
authors.initials: AT
authors.lastname: Pham
authors.forename: Hoa Anh
authors.initials: HA
authors.lastname: Nguyen
authors.forename: Tuan-Nghia
authors.initials: TN
authors.lastname: Phan
authors.forename: Simon M
authors.initials: SM
authors.lastname: Cutting
mesh_terms: D000327:Adsorption; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000737:chemistry; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D013171:Spores, Bacterial / Q000235:genetics / Q000378:metabolism; D019809:Streptavidin / Q000008:administration & dosage* / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001426:Bacterial Proteins; C439051:CotB protein, Bacillus subtilis; D004337:Drug Carriers; D019809:Streptavidin; D066246:ErbB Receptors; D017239:Paclitaxel; D000068818:Cetuximab