Combinatorial Photothermal and Immuno Cancer Therapy Using Chitosan-Coated Hollow Copper Sulfide Nanoparticles

Abstract

Near-infrared light-responsive inorganic nanoparticles have been shown to enhance the efficacy of cancer photothermal ablation therapy. However, current nanoparticle-mediated photothermal ablation is more effective in treating local cancer at the primary site than metastatic cancer. Here, we report the design of a near-infrared light-induced transformative nanoparticle platform that combines photothermal ablation with immunotherapy. The design is based on chitosan-coated hollow CuS nanoparticles that assemble the immunoadjuvants oligodeoxynucleotides containing the cytosine-guanine (CpG) motifs. Interestingly, these structures break down after laser excitation, reassemble, and transform into polymer complexes that improve tumor retention of the immunotherapy. In this “photothermal immunotherapy” approach, photothermal ablation-induced tumor cell death reduces tumor growth and releases tumor antigens into the surrounding milieu, while the immunoadjuvants potentiate host antitumor immunity. Our results indicated that combined photothermal immunotherapy is more effective than either immunotherapy or photothermal therapy alone against primary treated and distant untreated tumors in a mouse breast cancer model. These hollow CuS nanoparticles are biodegradable and can be eliminated from the body after laser excitation.

Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy

“…Plasmacytoid dendritic cells were then recruited and activated through activation of toll-like receptor 9 signaling, thus initiating effective and systemic antitumor immunity through a complicated immune cascade. Previous studies showed that CpG could effectively activate dendritic cells and elicit adaptive immune responses in vivo [37]. Here, histological analysis of 4T1 tumors following intravenous administration of GNR-PEI/CpG-laden-macrophages plus laser treatment revealed a dramatic infiltration of dendritic cells (CD11c + , 14.78%) in tumor sites compared with PBS (3.49%) and GNR-PEI/CpG-laden-macrophages without laser group (10.23%).…”

Perfluoropentane-Encapsulated Hollow Mesoporous Prussian Blue Nanocubes for Activated Ultrasound Imaging and Photothermal Therapy of Cancer

“…So far, several kinds of photothermal-conversion agents have been explored, including various gold nanostructures (e.g., nanostars, nanocages, nanoshells, nanorods, 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 4 bellflowers), 20-24 carbon nanomaterials (carbon nanotubes, graphene oxide, etc. ), [25][26][27][28][29][30][31] copper chalcogenides, [32][33][34][35][36][37] defective tungsten oxide nanomaterials (nanorods, nanowires), [38][39][40][41] Due to the strong NIR light absorption and high photothermal-conversion efficiency, PB NPs have been synthesized as a contrast agent for enhanced photoacoustic tomography, 11and a photothermal-conversion agent for PTT with photothermal stability. 14 Benefiting from the features of non-invasiveness, excellent soft-tissue resolution, real-time imaging, high safety and convenience, USimaging has been widely accepted for clinical diagnosis.…”

Copper sulfide nanoparticles: from synthesis to biomedical applications

“…CuS NP-based photothermal therapy could also be combined with immunotherapy. In an interesting design [11], chitosan-coated hollow CuS NPs were assembled with immunoadjuvants (CpG motifs) to construct a…”