Abstract 1719: Drug-loaded porphyrin nanoparticles as a platform for targeted and photodynamic combination therapy

Many traditional nanoparticle delivery mechanisms require the use of an inert vehicle to deliver single therapeutic payloads. Here, we describe a novel, dual-therapeutic, self-assembled nanoparticle class wherein both the payload and encapsulating vehicle may potentiate anti-neoplastic effects. The nanoparticles consist of photoactive porphyrin dyes encapsulating small molecule drugs. We screened 9 porphyrins with 27 small molecules for the formation of porphyrin-drug nanoparticles; a total of 243 nanoparticle candidates, of which 25 formed nanoparticles as dictated by pre-determined cutoffs for size, polydispersity, and porphyrin/drug concentrations. Logistic regression based on formation data and molecular descriptors suggested that the presence of electronegative groups positively influenced nanoparticle formation. Chemical inhibition of various uptake pathways in endothelial cells indicated that the uptake of these porphyrin-drug nanoparticles is largely mediated by clathrin and macropinocytosis. Stability testing demonstrated that porphyrin-drug nanoparticles remained stable at 37°C for at least 6 hrs. This work outlines the synthesis and characterization of a new class of porphyrin nanoparticles with the capacity to deliver targeted therapy. Furthermore, the simplicity of the self-assembly process highlights the potential for this novel nanoparticle paradigm to be easily tested in disease models. Citation Format: Justin M. Cheung, Hanan Baker, Daniel Li, Daniel Stor, Daniel A. Heller. Drug-loaded porphyrin nanoparticles as a platform for targeted and photodynamic combination therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1719.