期刊
ACS APPLIED MATERIALS & INTERFACES
卷 12, 期 38, 页码 42499-42510出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c10781
关键词
cancer immunotherapy; mesoporous silica; NIR-responsive drug delivery; polydopamine nanoparticles; photothermal therapy
资金
- National Institutes of Health [R21 CA236652, R01 CA141521]
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.
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