Metallocages represent a group of novel inorganic structures achieved by controlled assembly of metal and organic building blocks. These structures usually have a well-defined cavity, which can encapsulate small molecules via host-guest interactions. This property has been recently recognized being suitable for drug delivery. However, metallocages usually have small sizes (&lt;10 nm) and carry high positive charges, which are not favorable for drug delivery. In this work, we formulated the metallocages into nanoparticles that not only retain their host-guest chemistry, but also overcome the above-mentioned drawbacks. Cisplatin, a widely used platinum-based anticancer agent, was employed here as a proof-of-concept. In particular, the Pt(IV) prodrug of cisplatin was synthesized carrying a fluorescein moiety, which can bind to the cationic metallocage in a 1:1 ratio via host-guest interactions. Such a host-guest complex tends to precipitate at sub mM concentrations in PBS, and an anionic block copolymer, methoxy polyethylene glycol-<i>block</i>-polyglutamic acid (MPEG-PGA), was added to stabilize the precipitation at a nanoscale. The resulted nanoparticles of the drug-loaded metallocages are around 80 nm in diameter with a zeta potential at -16 mV. Furthermore, the nanoparticles can slowly release the therapeutic content and exhibit <i>in vitro</i> efficacy comparable to cisplatin.

Nanoprecipitation of metallocages for platinum-based anticancer drug delivery

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.