Self-Assembling NIR-Responsive Recombinant Protein Complex Nanoparticles for Synergistic Treatment of Malignant Tumors

Malignant tumor is a leading cause of human death and disability. The traditional monotherapies are often associated with inevitable side effects and result in severe tumor recurrence. Synergistic therapy that integrates multiple functions has provided a prospective direction, offering maximum anti-tumor efficiency and recurrence inhibition. Here, we developed an NIR-light-responsive recombinant proteinic complex nanoparticle due to the confined environment induced by the self-assembly of multicomponent supramolecular interactions. The pharmacological half-life was increased threefold by the synergy effect in the nanocomplex. The photo-thermal efficiency as high as 67.57% was realized, preventing the heat-related collateral damage with mild NIR irradiation. Compared with the pristine drug and other photothermal counterparts, the nanoassembly system demonstrated a long-acting and effective synergistic therapy against tumors. Upon direct peritumoral injection of the nanoparticle and with the 808 nm laser irradiation treatment, tumors were eradicated and no recurrence was observed. Furthermore, off-target side effects such as liver and kidney toxicity and immunogenicity were significantly mitigated with the nanoparticles. Additionally, nanoparticles can promote the maturation of neuron cells by increasing the density of dendrites or synapses when co-cultured in vitro, which might potentially reduce cosmetic defects and dysfunction to some extent. Taking advantage of its excellent biocompatibility, long-term stability, and long-acting chemo- and synergistic photothermal therapeutic effects, it has great potential in the clinical treatment of malignant tumors.