A Physiochemical, and Comparative Analysis of Verteporfin-Lipid Conjugate Formulations: Solid Lipid Nanoparticles and Liposomes

Visudyne, a liposomal formulation of verteporfin (benzoporphyrin derivative; BPD), is the only nanomedicine approved to date for photodynamic therapy (PDT). We have previously demonstrated that BPD conjugated to the lysophospholipid 1-arachidoyl-2-hydroxy--glycero-3-phosphocholine (BPD-PC) exhibits the greatest physical stability in liposomes, while maintaining cancer cell phototoxicity, from a panel of BPD lipid conjugates evaluated. In this study, we prepared 1,2-dipalmitoyl--glycero-3-phosphocholine (DPPC)-based solid lipid nanoparticles (LNPs) that stably entrap BPD-PC, which resemble the composition of the Spikevax Moderna COVID-19 vaccine, and compared them to a DPPC based liposomal formulation (). We evaluated the photochemical, optical, and phototherapeutic properties of both formulations. We also investigated the distribution and tumor microdistribution of both formulations. Our results demonstrated that is able to generate 17% more singlet oxygen than , while interestingly, is able to produce 76% more hydroxyl radicals and/or peroxynitrite anion. Importantly, only 28% of BPD-PC leaches out of the formulation during 7 days of incubation in serum at 37 °C, while 100% of BPD-PC leaches out of the formulation under the same conditions. Despite these differences, there was no significant difference in cellular uptake of BPD-PC or phototoxicity in CT1BA5 murine pancreatic cancer cells (derived from a genetically engineered mouse model). Interestingly, PDT using was more efficient at inducing immunogenic cell death (calreticulin membrane translocation) than when using IC and IC PDT doses. studies revealed that CT1BA5 tumor fluorescence signals from BPD-PC were 2.41-fold higher with than with ; however, no significant difference was observed in tumor tissue selectivity or tumor penetration. As such, we present as a unique and more stable nanoplatform to carry BPD lipid conjugates, such as BPD-PC, with a potential for future photodynamic immune priming studies and multiagent drug delivery.