Fabrication of near-infrared-light-responsive photothermal tea leaf-derived particles with thermotolerance inhibitory and anticancer activities.

Photothermal therapy (PTT) combined with chemotherapy is a promising cancer treatment approach, but its effectiveness is limited due to concerns about heat resistance mediated by heat shock proteins (HSPs) and the side effects of chemotherapy. In this study, we developed indocyanine green (ICG)-encapsulated tea leaf nanoparticles (TLNPs-ICG) as a photothermal nanoplatform. The TLNPs, approximately 140 nm in diameter, efficiently encapsulated ICG and demonstrated stable, concentration-dependent photothermal heating under 800 nm near-infrared irradiation. TLNPs-ICG were readily internalized by keratinocytes and melanoma cells, likely via the EGCG/67 kDa laminin receptor, and exhibited selective cytotoxicity against melanoma cells. When combined with near-infrared irradiation, TLNPs-ICG exhibited potent photothermal cell killing, whereas TLNPs or free ICG alone was only marginally effective. Importantly, TLNPs-ICG attenuated the upregulation of HSP70 and HSP90 and suppressed the acquisition of thermotolerance in vitro and in vivo. In a B16 melanoma mouse model, the intratumoral administration of TLNPs-ICG, combined with intermittent near-infrared irradiation, significantly suppressed tumor growth without apparent systemic toxicity. These results suggest that TLNPs-ICG are plant-derived biomaterials that integrate EGCG-mediated biochemical activity, heat shock regulation, and ICG-mediated photothermal effects, providing a platform for next-generation PTT-combined cancer therapy.