Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 46, Pages 43393-43408Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b17137
Keywords
photothermal therapy; immunogenic cell death (ICD); chemoimmunotherapy; tumoral inflammatory microenvironment activation; distant and deep-seated tumor
Funding
- National Natural Science Foundation of China [21701034, 21877051, 81803027]
- Planned Item of Science and Technology of Guangdong Province [2016A020217011]
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Inducing immunogenic cell death (ICD) that enhances the immunogenicity of dead cancer cells is a new strategy for tumor immunotherapy, but efficiently triggering ICD is the biggest obstacle to achieving this strategy, especially for distant and deep-seated tumors. Here, a new therapeutic system (Pd-Dox@TGMs NPs) that can effectively trigger ICD by combining chemotherapy and photothermal therapy was designed. The nanosystem was fabricated by integrating doxorubicin (Dox) and a photothermal reagent palladium nanoparticles (Pd NPs) into amphiphile triglycerol monostearates (TGMs), which showed specific accumulation, deep penetration, and activation in response to the tumoral enzymatic microenvironment. It was proved that codelivery of Dox and Pd NPs not only effectively killed CT26 cells through chemotherapy and photothermal therapy but also promoted the release of dangerous signaling molecules, such as high mobility group box 1, calreticulin, and adenosine triphosphate, improving the immunogenicity of dead tumor cells. The effective ICD induction mediated by Pd-Dox@TGMs NPs boosted the PD-L1 checkpoint blockade effect, which efficiently improved the infiltration of toxic T lymphocytes at the tumor site and showed excellent tumor treatment effects to both primary and abscopal tumors. Therefore, this work provides a simple and effective immunotherapeutic strategy by combining chemical-photothermal therapy to enhance immune response.
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