Polydopamine-Mesoporous Silica Core-Shell Nanoparticles for Combined Photothermal Immunotherapy.
Cancer immunotherapy involves a cascade of events that ultimately leads to cytotoxic immune cells effectively identifying and destroying cancer cells. Responsive nanomaterials, which enable spatiotemporal orchestration of various immunological events for mounting a highly potent and long-lasting antitumor immune response, are an attractive platform to overcome challenges associated with existing cancer immunotherapies. Here, we report a multifunctional near-infrared (NIR)-responsive core-shell nanoparticle, which enables (i) photothermal ablation of cancer cells for generating tumor-associated antigen (TAA) and (ii) triggered release of an immunomodulatory drug (gardiquimod) for starting a series of immunological events. The core of these nanostructures is composed of a polydopamine nanoparticle, which serves as a photothermal agent, and the shell is made of mesoporous silica, which serves as a drug carrier. We employed a phase-change material as a gatekeeper to achieve concurrent release of both TAA and adjuvant, thus efficiently activating the antigen-presenting cells. Photothermal immunotherapy enabled by these nanostructures resulted in regression of primary tumor and significantly improved inhibition of secondary tumor in a mouse melanoma model. These biocompatible, biodegradable, and NIR-responsive core-shell nanostructures simultaneously deliver payload and cause photothermal ablation of the cancer cells. Our results demonstrate potential of responsive nanomaterials in generating highly synergistic photothermal immunotherapeutic response.
['Seth|Anushree|A|http://orcid.org/0000-0003-2995-2200', 'Gholami Derami|Hamed|H|', 'Gupta|Prashant|P|', 'Wang|Zheyu|Z|', 'Rathi|Priya|P|', 'Gupta|Rohit|R|', 'Cao|Thao|T|', 'Morrissey|Jeremiah J|JJ|http://orcid.org/0000-0002-9911-4811', 'Singamaneni|Srikanth|S|http://orcid.org/0000-0002-7203-2613']
D000634:Aminoquinolines D000818:Animals D000970:Antineoplastic Agents D002470:Cell Survival D005260:Female D007093:Imidazoles D007155:Immunologic Factors D007167:Immunotherapy D007211:Indoles D008545:Melanoma D051379:Mice D008810:Mice, Inbred C57BL D053758:Nanoparticles D010316:Particle Size D000082703:Photothermal Therapy D011108:Polymers D012822:Silicon Dioxide D013499:Surface Properties D014407:Tumor Cells, Cultured
cancer immunotherapy polydopamine nanoparticles mesoporous silica NIR-responsive drug delivery photothermal therapy