Controlled Release of DNA Binding Anticancer Drugs from Gold Nanoparticles with Near-Infrared Radiation.

Traditional chemotherapies target rapidly developing cells in the human body resulting in harsh side effects including fatigue, immune system suppression, and nausea, among others. Delivery systems to focus the active pharmaceutical ingredients (APIs) to the diseased tissue can diminish the negative side effects while improving treatment outcomes. Gold nanoparticles (AuNP) offer many unique advantages as drug delivery vehicles, including being biologically inert, easily adaptable to various shapes and sizes, able to create a strong Au-thiol bond, and able to generate heat upon the absorption of near-infrared light. To this end, a AuNP delivery vehicle was engineered to load and release two DNA binding anti-cancer drugs, mithramycin and doxorubicin, in a controlled fashion. The drugs were loaded onto the surface of the AuNP with temperature sensitive linkages. The amount of heat generated, and subsequent release of the drugs was controlled by the irradiation time with a near-infrared laser. By modulating the linkage used to load the drugs three different release profiles were able to be achieved, indicating the feasibility of such a system for combinational therapy requiring sequential release of APIs.

Cyanuric chloride as the basis for compositionally diverse lipids.

Cyanuric chloride has been utilized in the development of new synthetic lipid compounds using two differing schemes. The resulting lipids, presented in this manuscript, were characterized and evaluated for their ability to form nanoparticles and subsequently tested for their utility in various biological applications, including gene delivery and immunization. Of the 12 lipids synthesized, 8 formed nanoparticles that remained stable, based on dynamic light scattering, for at least one month. The compounds were then assessed for their toxicity, and subsequently tested for their ability to encapsulate drugs, genes and peptides. While the compounds did not seem to encapsulate carboxyfluorescein, we demonstrate that these lipids are capable of plasmid delivery in vitro, and inducing antibody profiles similar to other hydrophobic anchors in liposomal peptide vaccines. This strategy for accessing diverse lipid compounds offers a way to easily optimize lipid-based therapeutics for research in an expedited manner.