Near-infrared light-triggered platelet arsenal for combined photothermal-immunotherapy against cancer

To address long-standing issues with tumor penetration and targeting among cancer therapeutics, we developed an anticancer platelet-based biomimetic formulation (N+R@PLTs), integrating photothermal nanoparticles (N) and immunostimulator (R) into platelets (PLTs). Exploiting the aggregative properties of platelets and high photothermal capacity, N+R@PLTs functioned as an arsenal by targeting defective tumor vascular endothelial cells, accumulating in a positive feedback aggregation cascade at sites of acute vascular damage induced by N-generated local hyperthermia, and subsequently secreting nanosized proplatelets (nPLTs) to transport active components to deep tumor tissue. The immunostimulator augmented the immunogenicity of antigens released from ablated tumors, inducing a stronger immunological response to attack residual, metastatic, and recurrent tumors. Following activation by low-power near-infrared light irradiation, the photothermal and immunological components synergistically provide exceptionally high therapeutic efficacy across nine murine models that mimicked a range of clinical requirements, and, most notably, a sophisticated model based on humanized mouse and patient-derived tumor xenograft.

Automated summary

The anticancer platelet-based biomimetic formulation developed in this study integrates photothermal nanoparticles and immunostimulator into platelets to target tumor cells effectively. By accumulating at tumor sites and releasing active components, this formulation induces a strong immune response against residual, metastatic, and recurrent tumors, showing exceptionally high therapeutic efficacy across various murine models.