Previous work in the Gianneschi lab has demonstrated that enzyme-responsive micellar nanoparticles are capable of a targeted accumulation and retention within tumor tissue in response to overexpressed matrix metalloproteinases. It has also been shown that small molecule therapeutics that were covalently bound to the nanoparticle scaffold could selectively be delivered to the site of disease. This targeted delivery method is, however, only applicable to molecules that can be conjugated to the polymer without altering the resulting overall micellar structure. We have developed an approach that enables the bioorthogonal conjugation of molecules onto micellar nanoparticles by the means of a tetrazine cycloaddition reaction. The synthesis of the polymer amphiphiles is facilitated by ring-opening metathesis polymerization (ROMP) followed by the conjugation of either a strained alkene or a tetrazine moiety. After the formulation of the polymers into spherical micelles, molecules of different sizes were successfully conjugated by the cycloaddition reaction onto the micelles. With this approach we aim to facilitate the <i>in vivo</i> labeling of assembled nanomaterials with any large molecule or therapeutic.

Bioorthogonal labeling of micellar nanoparticles

251st National Meeting (2016)

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