Bioconjugates comprising nanoparticles and aptamers represent a potentially powerful tool for developing novel diagnostic and therapeutic modalities for cancer detection and treatment. As drug delivery vehicles for cancer therapy, nanoparticle-aptamer bioconjugates can be designed to target and be taken up by cancer cells for targeted delivery and controlled release of chemo-therapeutic drugs over an extended time directly at the site of tumors. The successful achievement of this goal requires the isolation of aptamers that bind to the extracellular domain of antigens expressed exclusively or preferentially on the plasma membrane of cancer cells or on the extra cellular matrices of tumor tissue. In addition, nanoparticles would have to be designed with the optimized properties that facilitate targeting and delivery of the drugs to the desired tissues while avoiding uptake by the mononuclear phagocytic system in the body.

The targeted delivery of chemotherapeutic drugs for cancer therapy may minimize their side effects and enhance their cytotoxicity to cancer cells, resulting in a better clinical outcome. We anticipate that the combination of controlled release technology and targeted approaches may represent a viable approach for achieving this goal. One major clinical advantage of targeted drug-encapsulated nanoparticle conjugates over drugs that are directly linked to a targeting moiety is that large amounts of chemotherapeutic drug may be delivered to cancer cells per each delivery and biorecognition event. Another advantage would be the ability to simultaneously deliver two or more chemotherapeutic drugs and release each in a predetermined manner, thus resulting in effective combination chemotherapy, which is common for the management of many cancers. Antibodies and peptides have been widely used for the targeted delivery of drug encapsulated nanoparticles; however, the translation of these vehicles into clinical practice has lagged behind our advances in the laboratory. This has been largely due to the immunogenicity and nonspecific uptake of nanoparticle-antibody bioconjugates by nontargeted cells, resulting in toxicity or poor efficacy of these conjugates. Nanoparticle-aptamer bioconjugates face some of the same challenges of nonspecific uptake after systemic administration and thus must be engineered with surface physicochemical characteristics to avoid toxicity to nontargeted cells. We believe that optimal particle size and surface properties to sufficiently decrease the rate of nonspecific particle uptake while achieving successful targeting must be determined experimentally on a case-by-case basis, as this also depends on the polymer system, the drug being encapsulated and the tumor microenvironment including its vascularity. However, the advantage of nanoparticle-aptamer bioconjugates over their antibody conjugate counterparts lies in the ease of aptamer isolation, lack of immunogenicity, and a decreased batch-to-batch variability attributable to the chemical nature of aptamer synthesis and production, which can facilitate the translation of optimally engineered nanoparticle-aptamer bioconjugates into clinical practice.

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