Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma

Abstract

In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA; INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma.

Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study

“…In this sense, biodegradable nanoparticles made of poly-D,L-lactic-co-glycolic acid (PLGA) may represent a suitable candidate to encapsulate DXI and deliver it slowly into the target tissue [4]. In addition, PLGA has been approved by the Food and Drug Administration and is one of the most successful biodegradable polymers [3][4][5][6]. Moreover, PEG has been widely used to reduce the clearance of PLGA nanoparticles (NPs) and it has been demonstrated that PEG coatings shield the surface from aggregation, opsonization, phagocytosis and prolong nanoparticles systemic circulation time [5].…”

Photothermal therapies to improve immune checkpoint blockade for cancer

“…A critical consideration in optimizing nanoparticle-based PTT for combination with ICB is finding the appropriate thermal dose. We have demonstrated that immunogenic cell death occurs at a specific thermal window, depending on the cancer type [43,50,52]. Table 2 presents the temperatures attained during PTT in different tumor models reviewed here.…”

“…Various organic dyes such as cyanine-based dyes (e.g., indocyanine green (ICG)) including heptamethine cyanines (e.g., IR825, IR780, IR808, IR2) and phthalocyanines (e.g., metallo-naphthalocyanines), diketopyrrolopyrrole-based agents, croconaine-based dyes, porphyrinbased dyes, polymer-based dyes (e.g., polypyrrole) have been used for PTT either as free agents or within nanoparticles. These formulations have been used alone and in combination with chemotherapy, radiation therapy, immunotherapies or therapies targeting epigenetic modulation [50,125,126]. Here, we review the latest studies using the organic dyes ICG, polydopamine and IR820 as PTT agents in combination with ICB.…”

Solutions to the Drawbacks of Photothermal and Photodynamic Cancer Therapy

“…Since PTT can induce antitumor immunity of the body, rational use and appropriate enhancement of body's antitumor immune process can be effective for tumor treatment. [ 59,62,63 ] In this case, Sun and coworkers [ 64 ] encapsulated a photothermal material, polydopamine (pDA), on the surface of attenuated Salmonella VNP20009 (pDA‐VNP) through the oxidative self‐polymerization in alkaline solution ( Figure ). Many kinds of immune cells participate in the therapy process.…”