# Triple-synergistic biomimetic nanoplatform orchestrates photothermal immunotherapy through coordinated ICD and STING activation

## TL;DR

A new biomimetic nanoplatform combines photothermal therapy and immune activation to effectively treat tumors and boost long-term immunity.

## Contribution

A triple-synergistic nanoplatform that integrates photothermal ablation, ICD, and STING activation for enhanced immunotherapy.

## Key findings

- The nanoplatform suppressed both primary and distant tumors in mice with a 4-fold increase in CD8+ T cells.
- It reprogrammed the tumor microenvironment to be pro-inflammatory and acted as a nanovaccine for durable protection.
- ICD and STING activation synergistically enhanced immune responses and systemic antitumor immunity.

## Abstract

The immunosuppressive tumor microenvironment (TME) impedes conventional cancer immunotherapies. To overcome this barrier, we engineer DDT-HM nanoparticles (NPs), a biomimetic nanoplatform cloaked in a hybrid membrane fused from cancer cells and macrophages. This dual-functional coating combines macrophage-mediated immune evasion for prolonged circulation with cancer cell-directed homologous targeting for precise tumor accumulation. DDT-HM NPs co-deliver a rationally designed NIR-II photothermal agent (TPT-Se) and a STING agonist (DMXAA). Under 808 nm irradiation, TPT-Se generates localized hyperthermia that directly ablates tumors and triggers immunogenic cell death (ICD), releasing damage-associated molecular patterns (DAMPs), including cytosolic DNA. Simultaneously, tumor-localized DMXAA potently activates the STING pathway. Crucially, ICD and STING signaling exhibit potent reciprocal reinforcement: ICD-derived DAMPs amplify dendritic cell (DC) maturation, which is further potentiated by STING-driven type I interferon responses, while STING activation amplifies ICD-initiated systemic antitumor immunity. In 4T1 tumor-bearing mice, this strategy achieves remarkable suppression of both primary and distant tumors, accompanied by a 4-fold increase CD8+ T cells and a pro-inflammatory TME reprogramming. Furthermore, DDT-HM NPs function as a potent nanovaccine, expanding central and effector memory T-cell pools and conferring durable protection against tumor rechallenge. This work establishes a “triple-threat” biomimetic platform that unifies precision photothermal ablation, synergistic dual-pathway immune activation, and nanovaccine functionality for durable cancer immunotherapy.

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