Investigation of active targeting of cancerous cells using antibody modified drug loaded protein nanoparticles

Introduction Nowadays, cancer is one of the most important causes of mortality all over the world. Albumin nanoparticles (NPs) have shown several advantages such as stability, biodegradability, nontoxicity, the possibility of scale up during manufacturing, etc. Active targeting, which uses affinity ligands on the surface of NPs, helps the specific retention and uptake by the targeted disease cells. Objectives The human epidermal growth factor receptor-2 (HER2) is overexpressed in breast, ovarian and gastric cancers. Therefore, the attachment of anti-HER2 monoclonal antibody (mAb) on the surface of albumin NPs helps the effective internalization of drug loaded NPs in HER2 positive tissues and increases the possibility of treatment in Drug Delivery Systems (DDSs). Methods Albumin NPs were synthesized by desolvation method. In order to investigate the optimum level of attached mAb, seven experiments were designed by Design Expert. Then, the amounts of mAb were conjugated to the surface of NPs with EDC/NHS crosslinkers. Targeted NPs were characterized and optimized, Gemcitabine loaded targeted NPs were produced and finally, were investigated on breast cancer cells by MTT assay. Results The size and zeta potential of albumin NPs were measured by DLS which obtained to be 156 ±17 nm and -31 ±4 mV, respectively. FTIR test verified the attachment of antibody to the surface of NPs and the optimum amount of antibody was found. Initial evaluations on target cells verified higher efficiency of treated NPs in cancer treatment. ConclusionThis study has demonstrated a specific binding and intracellular accumulation of anti-HER2 mAb-coupled BSA nanoparticles loaded with anticancer drug, gemcitabine. Employment of this targeted delivery system was able to enhance the therapeutic effect of drugs on HER2-positive cells.

کلیدواژه ها:

HER2 ، Albumin nanoparticles ، Monoclonal antibody ، Drug delivery system ، Breast cancer