Enhancing the Cytotoxicity of Chemotherapeutics with Gold Nanoparticle Delivery

X. Zhang, J. Dostie, J. Teodoro, J. Nadeau
McGill University, CA

Keywords: doxorubicin, gold nanoparticles, drug delivery

Summary:

Doxorubicin is one of the key chemotherapeutics in current cancer treatments. However, its application is still limited to melanoma due to its strong inherent resistance to therapeutics. This resistance mechanism rises from constant drug efflux, melanosomal quenching, enhanced cell self-repair system and etc. Therefore, modification of Doxorubicin (Dox) to overcome this difficulty will not only enhance its clinical efficacy but also reduce the cost of new drug research and development. In this work, we developed a drug delivery system involving gold nanoparticles to address this problem. As presented in our previous publication, there was almost a 20-fold increase of the Dox cytotoxicity in vitro when delivered by ultrasmall gold nanoparticles (2.8nm). This surprising enhancement has undergone phenotypic analysis, which showed that gold nanoparticles could deliver Dox directly to the nucleus at high speed, as well as escape the constant exportation by ABC-transporter. The current in-vivo experiment indicated that the nanoparticle delivered Dox were also able to significantly reduce the growth rate of B16 melanoma tumor, one most aggressive form of cancer models. A genome-wide loss-of-function screen should help unveil how the gold Dox conjugates overcame this resistance on a genotypic level.