Engineering an Organic Nanoplatform for Augmented Pyroeletroimmunotherapy.

Photothermal immunotherapy has shown great promise in the treatment of tumor metastasis. However, the thermal resistance of tumor cells substantially compromises the treatment effect of photothermal immunotherapy. Herein, a high-performance organic pyroelectric nanoplatform, t Bu-TPAD-BF 2 nanoparticles (NPs), was rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible t Bu-TPAD-BF 2 NPs with excellent pyroelectric and photothermal conversion properties were constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with t Bu-TPAD-BF 2 NPs caused an apparent temperature elevation upon near-infrared (NIR) laser irradiation, inducing potent immunogenic cell death (ICD). Additionally, the temperature variations under alternating NIR laser irradiation facilitated reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrated that t Bu-TPAD-BF 2 NPs in combination with NIR laser exposure notably inhibited primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling revealed that treatment with t Bu-TPAD-BF 2 NPs markedly suppressed metastasis under NIR laser illumination by downregulating metastasis-related genes and upregulating immune response-associated pathways. Therefore, this study provides a strategy for designing high-performance pyroelectric nanoplatforms to effectively cure tumor metastasis, thereby overcoming the inherent shortcomings of photothermal immunotherapy. This article is protected by copyright. All rights reserved.