Docetaxel loaded human serum albumin nanoparticles: Synthesis, characterization and potential of nuclear imaging of prostate cancer

The second most common type of cancer in men in our country is prostate cancer. Well-time clinical treatment and imaging have critical importance for an effective therapy system in the cancer treatment. Depending on the stages of cancer and its localization, the cancer treats with applications such as surgery, chemotherapy and radiotherapy. However these treatment methods damage normal cells and cause various side effects. The chemotherapy and radiotherapy methods are the most frequently used methods in the treatment of cancer despite their side effects. Most cancer drugs used for chemotherapy cannot separate tumor cells from healthy cells. Therefore, it causes systemic toxicity and side effects. This situation limits the maximum available dose of the drug. In addition, rapid elimination and spread over a large area require a greater amount of the drug applied. In addition to not being economical, it causes undesirable side effects. In this study, the anticancer drug loaded nanoparticles were prepared and labeled with 131I for diagnosis and treatment of prostate cancer. Human serum albumin nanoparticles (HSA) with hydrodynamic diameter of 90 nm and a zeta potential of 52.6 mV were synthesized as drug delivery system. According to results of SEM analysis, the size of spherical HSA nanoparticles was mesaured to be in the range of 100-200 nm. HSA nanoparticles are aimed to provide transport of the anticancer drug to the target tissue. Docetaxel (DTX) were loaded onto the nanoparticles with 50% efficiency. The size of DTX loaded nanoparticles (DTX-HSA) is in the range of 150-160 nm and these nanoparticles have a zeta potential of -27.2 mV. According to results of SEM analysis, the size of DTX-HSA nanoparticles were determined as the range of 150-300 nm. The results of FTIR analysis support that syntheses of HSA nanoparticles and DTX-HSA nanoparticles were successfully carried out. According to in vitro drug release assay, 80% of DTX from loaded DTX-HSA nanoparticles was released at pH 7.4 medium, while 93% of DTX was released from DTX-HSA nanoparticles at pH 5.8 medium in the end of 48 hours. DTX-HSA nanoparticles were labelled with 131I via iodogen method. According to quality control studies the labelling efficiency was 98.67±2.31%. In vitro intracellular uptake experiments of 131I-DTX-HSA nanoparticles was done on prostate tumor cells (PC-3) (1.29±0.22%) and healthy prostate cells (RWPE-1) (0.65±0.17%) at 24 hours. 131I-DTX-HSA nanoparticles uptake is higher in PC-3 cell line than RWPE-1 cell line. The highest uptake in PC-3 cell line was observed in 24 hours incubation time, the uptake value reduced in incubation time increased. It is observed that toxic effect on healthy cells decreases by selective accumulation of DTX anticancer drug loaded nanoparticles in tumor cells compared to healthy cells thanks to drug delivery system. Thus the side effects of the drug decreased. It is put forth that use of DTX-HSA nanoparticles in the treatment of prostate cancer has been proven to be a more effective therapy. Obtained results shown that DTX-HSA nanoparticles are labelled with 131I with high efficiency and might be useful in nuclear imaging of prostate cancer. Moreover the 131I-DTX-HSA nanoparticles may be contribute treatment of the cancer as it has a β- emission of 131I as well as γ emission. In conclusion, 131I-DTX-HSA appears as suitable agent that might be used in both nuclear imaging and radiotherapy of prostate cancer. In this study the nuclear imaging potential of 131I-DTX-HSA was determined as in vitro. The results of study are important to be based on investigating of this potential with in vivo studies in the future. Key words: Human serum albumin (HSA), docetaxel, prostate cancer, 131I