Combination cancer treatments directed towards different molecular targets can yield higher therapeutic efficacy with reduced side effects. In this report, we describe a combination regimen that leverages advancements in photodynamic therapy, drug delivery and targeted agents for multiple pathways achieved via a photoactivatable multi-inhibitor nanoliposomes (PMILs) for photodynamic tumor cell and microvessel damage. The PMIL is a biodegradable delivery system comprised of PEG-PLGA nanoparticle loaded with the c-MET/VEGFR2 inhibitor (cabozantinib, XL184) encapsulated within a liposome containing the lipid-associated photosensitizer (benzoporphyrin derivative monoacid A, BPD). Following intravenous PMIL administration, near infrared irradiation of tumors triggers photodynamic therapy and initiates drug release from the nanoparticle. Interestingly, a single dose of PMIL mediated combination therapy achieves sustained tumor reduction with suppression of metastatic escape. In contrast, combination therapy by co-administration of the individual agents has significantly reduced impact. Furthermore, conventional XL184 administration requires several treatment cycles to achieve the same effect. The PMIL light-regulated combination strategy has demonstrated a unique combination treatment delivery approach using a single nanoconstruct. Furthermore, this concept can be made amenable to a number of molecular inhibitors and offers new prospects for spatiotemporal synchronization of combination therapies while reducing systemic drug exposure and associated toxicities.

Light activation and triggered drug release of multi-agent loaded nanoconstructs for simultaneous suppression of multiple treatment escape pathways in the pancreatic cancer

253rd National Meeting (2017)

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