Figure 1.

Hypothesized mechanism of action of our approach combining photothermal and epigenetic therapy for melanoma using poly (lactic-co-glycolic acid) (PLGA) nanoparticles. The photothermal agent, indocyanine green (ICG), and the epigenetic drug, Nexturastat A (NextA), were co-encapsulated within PLGA nanoparticles (ICG-Next A-PLGA; INAPs). The INAPs were administered to melanoma tumors in syngeneic murine models and activated with an 808 nm near infrared laser. ICG-based photothermal therapy along with concurrent epigenetic drug (NextA) release in the tumor microenvironment causes tumor cell death and increased immunogenicity, which we expected to slow tumor growth and improve survival in melanoma when compared to either therapy alone. Further, since PLGA is biodegradable, we expected our INAP platform to mitigate toxicity concerns associated with the long-term persistence of nanoparticles in vivo.