Correlation between cell survival, clonogenic activity and micronuclei induction in DMBA-OC-1R cells treated with immunospecific albumin microspheres containing cisplatin and 5-fluorouracil.
An ideal chemotherapeutic strategy would be to deliver a high concentration of drug that would be released in sustained small amounts from targeted microspheres to effectively kill only the tumour cells and thus reduce toxicity to normal tissue. Clonogenic and cell survival growth curve assays, as well as the micronucleus assay, were used to determine the feasibility of employing targeted immunomicrospheres in the treatment of cancer. Cells of a rodent ovarian carcinoma cell line, were exposed to cisplatin and 5-fluorouracil, either as free drug or encapsulated in albumin microspheres that were either conjugated to monoclonal antibodies or not. In cell survival growth curve assays, cell survival was reduced to 1.2% of the control when cells were treated with drug-containing immunomicrospheres. 3.2-fold more micronuclei were found in those cells that had been exposed to the drugs in immunomicrospheres than in those subjected to untargeted microspheres. All three assays demonstrated that the targeted immunomicrospheres were more effective in delivering cisplatin and 5-fluorouracil directly to the cells than the unconjugated microspheres, thus suggesting that targeted chemotherapy might be a more effective option in the treatment of cancer.
Truter
Ernest J
EJ
Faculty of Applied Sciences, Cape Technikon, Cape Town, South Africa. etruter@ctech.ac.za
Santos
Aldina S
AS
Els
Willem J
WJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000418:Albumins / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use*; D002999:Clone Cells / Q000187:drug effects* / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012377:Rodentia; D014407:Tumor Cells, Cultured
D000418:Albumins; D002945:Cisplatin; D005472:Fluorouracil