Aptamers in prostate cancer in vivo research
Prostate cancer is the most common cancer among men, with approximately 1.1 million new cases diagnosed per year worldwide. Most cancer-related deaths are caused by metastases in vital organs, with bones among the most frequent sites of prostate cancer metastases.
So far, various synthetic carriers have been developed to form compact nano-sized complexes carrying cancer therapeutics to specific tumor lesions. However, the side effects caused by off-target effects have resulted in a low therapeutic index and poor safety profiles. One promising approach is to transport drugs to their specific target destinations, shielding the drugs from elimination and degradation in the process of overcoming biological barriers. Aptamers have become a promising targeting tool in the development of targeted delivery systems because of their unique binding properties. This proves them advantageous over antibodies including fast tissue penetration, non-immunogenicity, and thermal stability.
In this view, Chen et al. explored the use of aptamers as promising tools to develop a targeted drug delivery system for prostate bone metastases (PB). In vivo SELEX was conducted to obtain aptamers with high binding affinity and specificity for mouse bone with PC3 PB. After ten rounds of in vivo SELEX, the PB aptamer with the highest hitting frequency was attained and analyzed in vitro and in vivo. Compared with the control aptamer, the PB aptamer exhibited high levels of accumulation in tumor mouse bone mediated by binding bone marrow endothelial cells. Moreover, the aptamer exhibited much higher levels of accumulation in the bone of tumor-bearing mice than healthy controls, indicating that the PB aptamer specifically targeted bone in tumor-bearing mice. These conclusions were supported by observations of bone sections under microscopy, as well as the high binding affinity of the PB aptamer for mouse tumor-exposed bone marrow endothelial cell ex vivo.
Moreover, PB aptamer could efficiently deliver therapeutics to the bone of mice with PC3 prostate bone metastasis. This was demonstrated by higher levels of Cy5-PB-Au particles in bone marrow compared with control Cy5-Au particles.
Overall, this investigation highlighted the promise of in vivo SELEX for the discovery of bone targeting aptamers for use in drug delivery. Beyond that, due to their excellent properties such as small size, high binding affinity, specificity, good biocompatibility, high stability, and low immunogenicity, aptamers contribute to their wide application in the biomedical field including cancer therapy. If you want to explore how aptamers can be used for your research, discovery and development projects then please contact us.
Reference: Chen L, He W, Jiang H, et al. In vivo SELEX of bone targeting aptamer in prostate cancer bone metastasis model. Int J Nanomedicine. 2018;14:149–159. Published 2018 Dec 21. doi:10.2147/IJN.S188003