Engineering an Organic Nanoplatform for Augmented Pyroeletroimmunotherapy

Abstract

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, ^tBu-TPAD-BF₂ nanoparticles (NPs), is rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible ^tBu-TPAD-BF₂ NPs with excellent pyroelectric and photothermal conversion properties are constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with ^tBu-TPAD-BF₂ NPs causes 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 facilitate reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrate that ^tBu-TPAD-BF₂ NPs in combination with NIR laser exposure notably inhibit primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling reveals that treatment with ^tBu-TPAD-BF₂ NPs markedly suppresses 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.

Keywords: immunogenic cell death; nanomedicine; organic pyroelectric nanoplatform; pyroelectroimmunotherapy; tumor therapy.