(497g) Efficient and Safe Delivery of Cancer Chemotherapeutics By DNA Fragments

Small molecule pharmaceutical treatment of cancer has several issues, including lack of bioavailability, insolubility, and systemic toxicity. While nano-scale drug delivery systems have risen to the challenge in overcoming issues faced by free small molecules by increasing the retention time of drugs and decreasing toxicity; issues of immunogenicity, non-biodegradability, and toxicity still remain due to the materials used in their manufacture. Furthermore, rarely are these nanoparticles produced without the incorporation of several intensive processes that end up making them expensive to synthesize and difficult to scale up for clinical or commercial use. In addition, disappointingly low therapeutic payload is a common concern. Thus, we looked towards natural biopolymers and wondered if it was possible to simply use nucleic acids themselves as a drug delivery vehicle for cancer chemotherapeutic delivery. DNA fragments are readily produced from a natural source and offer the desired properties for the delivery of small molecule therapeutics. A model cancer chemotherapeutic was complexed with DNA fragments in a scalable and cost-effective manner. The resulting nano-scale complexes demonstrated improved anti-cancer efficacy with substantially lowered toxicity in vitro and in vivo, in comparison with free drug and a commercially available liposomal formulation. This talk also highlights the characterization of the complexes at a molecular level and a mechanistic study on the complexes’ interactions with cancer cells in vitro and in vivo. The results of this study encourage an elegant and simple approach to drug formulation that utilizes the natural properties of nucleic acids to address the fundamental challenges in cancer chemotherapy. Finally, our new formulation may offer immediate implications for rapid clinical translation and commercialization.