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

• Published in: ACS nano Vol. 8; no. 6; pp. 5670 - 5681
• Main Authors: Guo, Liangran, Yan, Daisy D, Yang, Dongfang, Li, Yajuan, Wang, Xiaodong, Zalewski, Olivia, Yan, Bingfang, Lu, Wei
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.06.2014
• Subjects: ABLATION; Animals; Antigens, Neoplasm - chemistry; Cancer; Chitosan - chemistry; COATINGS; Copper - chemistry; COPPER SULFIDE; CpG Islands; Cytokines - metabolism; Excitation; Female; Hyperthermia, Induced - methods; Immunotherapy - methods; Infrared Rays; LASERS; Light; Metal Nanoparticles - chemistry; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; MICROSTRUCTURES; Nanoparticles; Nanostructure; Nanotechnology - methods; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - therapy; Oligonucleotides - chemistry; PARTICLES; Phototherapy - methods; SULFIDES; Sulfides - chemistry; Therapy; Tumors; photothermal; cytosine-guanine; cancer; hollow CuS nanoparticle; immunotherapy
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/nn5002112

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.