Aptamer-Functionalized Nanoparticles as "Smart Bombs": The Unrealized Potential for Personalized Medicine and Targeted Cancer Treatment

Conventional delivery of chemotherapeutic agents leads to multiple systemic side effects and toxicity, limiting the doses that can be used. The development of targeted therapies to selectively deliver anti-cancer agents to tumor cells without damaging neighboring unaffected cells would lead to higher effective local doses and improved response rates. Aptamers are single-stranded oligonucleotides that bind to target molecules with both high affinity and high specificity. The high specificity exhibited by aptamers promotes localization and uptake by specific cell populations, such as tumor cells, and their conjugation to anti-cancer drugs has been explored for targeted therapy. Advancements in the development of polymeric nanoparticles allow anti-cancer drugs to be encapsulated in protective nonreactive shells for controlled drug delivery with reduced toxicity. The conjugation of aptamers to nanoparticle-based therapeutics may further enhance direct targeting and personalized medicine. Here we present how the combinatorial use of aptamer and nanoparticle technologies has the potential to develop "smart bombs" for targeted cancer treatment, highlighting recent pre-clinical studies demonstrating efficacy for the direct targeting to particular tumor cell populations. However, despite these pre-clinical promising results, there has been little progress in moving this technology to the bedside.