Reversing tumor to “Hot”: A NIR light-triggered carrier-free nanoplatform for enhanced tumor penetration and photo-induced immunotherapy

Immunogenic cell death (ICD) process associated with phototherapy is a promising strategy to inhibit tumor growth and metastasis. To facilitate deep tumor-penetrating photo-immunotherapy, we herein report a near-infrared (NIR) light-triggered carrier-free nanoplatform (IR837) loaded with indocyanine green (ICG) and immune adjuvant R837. The IR837 nanoparticles were prepared as carrier-free nanoassembly and showed good photostability. With the thermal-responsive polydopamine as the shell, the IR837 (∼78 nm) can efficiently disassociate into smaller size (∼10 nm) under NIR irradiation. Through intravenous injection, IR837 displays prolonged blood circulation and turns into the smaller-sized nanoaggregates to deeply penetrate in the core sites of tumors. The ICD process is then induced and results in dendritic cells (DCs) maturation to initiate the immune response. Eventually, the “cold” tumor would be reversed into the “hot” tumor, promoting the immunotherapeutic outcomes against in-situ and distal tumors under mild temperature (45 °C). In summary, our research provides a prospective intelligent nanodelivery system to perform efficient photothermal immunotherapy against primary and distal tumor growth with hopefully low side effect.