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 lesion. However, the side effects caused by off-target effects have resulted in 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 system 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 prostrate 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 (Figure 1A). Compared with control aptamer, the PB aptamer exhibited high levels of accumulation in tumor mouse bone mediated by binding with bone marrow endothelial cell (1B). Moreover the aptamer exhibited much higher levels of accumulation in bone of tumor-bearing mice than healthy controls, indicating that the PB aptamer specifically targeted bone in tumor-bearing mice (1C and D). These conclusions were supported by observations of bone sections under microscopy, as well as high binding affinity of the PB aptamer for mouse tumor-exposed bone marrow endothelial cell ex vivo.

Figure 1. In vivo SELEX of bone targeting aptamer in nude mice bearing PC3 PB. (A) In vivo SELEX procedures (B) Higher binding affinity of PB aptamer to bone marrow endothelial cell compared with control aptamer ex vivo. (C) & (D) Higher accumulation of the PB aptamer in bone of tumor mouse compared with the control aptamer, more accumulation of the PB aptamer in bone of tumor mice compared with healthy mice.

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 particle (figure 2).

Figure 2. (A) Cy5-PB-Au particle under fluorescence microscopy. (B) Accumulation of a few Cy5-Au particles within tumor in bone marrow and marked accumulation of Cy5-PB-Au particle within tumor in bone marrow (red: Cy5-Au/Cy5-PB-Au particle; blue: nuclei) (C) Co-localization of Cy5-PB-Au particle with a vascular endothelial cell marker within tumor in bone marrow (red: Cy5-PB-Au particle; green: CD31; blue: nuclei).

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 biomedical field including cancer therapy. If you want to explore on how aptamers can be used for your research, discovery and development projects then please contact us using the form below.

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