In traditional photothermal therapy (PTT), the collateral damage to surrounding normal tissues caused by strong laser radiation, and the cellular anti-apoptosis and cytoprotection mechanisms of cancer cells in mild hyperthermia PTT, severely limit the therapeutic efficacy of tumor treatment. Here, we present a targeted folic acid-modified Au-Ag nanoparticle-nanowire construct (FA-Au-Ag NPs-NW) that specifically targets and binds to the folate receptor-overexpressing membranes of cancer cells. This construct enables efficient high-density nanoscale photothermal conversion under mild conventional LED irradiation, a property derived from the enhanced local surface plasmon resonance (LSPR) effect of the bimetallic Au-Ag heterostructure. Both in vitro and in vivo studies demonstrate that the construct avoids collateral damage to normal tissues, effectively inhibits the cellular anti-apoptotic and cytoprotective pathways, and induces tumor cell apoptosis through light-matter interactions, without the need for therapeutic drugs. This work offers a promising strategy for tumor treatment and broadens the application of LED-induced mild-temperature PTT for disease management. Scheme 1. LED light inhibits malignant tumors via high-density nanolocalized photothermal effects on cell membranes. A) Schematic illustration of the construction of FA-Au-Ag NPs-NW. B) Schematic illustration of targeting tumor cells via folic acid and folic acid recipient interaction in the cytomembrane. C) Under the illumination of LED light, a high-density nano-local field is generated on the surface of the nanowires, achieving high-efficiency photothermal conversion. D) The high-density photothermal conversion nano-regions are closely attached to the cell membrane, causing photothermal damage to the cells and thereby leading to the apoptosis of tumor cells. This work presents a folic acid (FA)-targeted FA-Au-Ag NPs-NW construct that selectively binds to cancer cell membranes and generates nanoscale photothermal effects through local surface plasmon resonance (LSPR) under LED irradiation. It avoids collateral damage to surrounding normal tissues—an issue inherent to strong laser-based PTT—and the activation of anti-apoptotic and cytoprotective pathways by cancer cells under mild hyperthermic conditions. Both in vitro and in vivo revealed that this nanoplatform exhibits significantly higher photothermal conversion efficiency in tumor cells and murine tumors compared to conventional counterparts, thereby validating the practical applicability of this approach. • Replacing high-energy lasers with low-energy LED light in photothermal therapy (PTT) avoids limitations like thermal resistance and side effects, enhancing specificity and safety. • Physical therapy boosts light-matter interactions to induce apoptosis, addressing the issue of incomplete tumor eradication by mild-temperature PTT alone. • Wavelength-insensitive, rapid nano-localization PTT with high conversion efficiency enables tumor inhibition without specialized lasers or drugs, potentially revolutionizing clinical access and allowing antitumor treatment wherever light is available.
Qi et al. (Fri,) studied this question.