Photothermal cancer treatment with laser-activated yolk-shell nanoparticles and synergistic combination of chemotherapy

Synergistic chemo-photothermal therapy is a robust and reliable strategy for the effective elimination of cancer cells. In this study, we introduce a developed therapeutic approach that integrates photothermal therapy (PTT) via yolk-shell gold nanoparticles (YS-GNP) with doxorubicin (DOX)-mediated chemotherapy to enhance anticancer efficacy. YS-GNP was meticulously engineered as a highly efficient photothermal agent, utilizing the localized surface plasmon resonance of gold nanoparticles within the yolk-shell structure. Upon near-infrared laser irradiation, YS-GNP effectively induced cancer cell death under mild hyperthermic condition. In vitro studies on HeLa and YD10B cancer cell lines demonstrated that the combination therapy (YS-GNP/DOX/Laser) significantly improved therapeutic outcomes compared to monotherapies, selectively targeting cancer cells while minimizing damage to normal cells. The enhanced anticancer effects were attributed to the complementary mechanisms of DOX-induced reactive oxygen species generation and YS-GNP-mediated lysosomal disruption. Furthermore, inhibition of heat shock proteins (HSPs) substantially amplified cancer cell death, highlighting the multifaceted mechanisms underlying the PTT approach. In particular, significant reductions in HSP70 expression (1.45-fold in YD10B, 1.96-fold in HeLa) and HSP90 expression (1.58-fold in YD10B, 5.88-fold in HeLa), support the synergistic anticancer effect and mechanism of DOX and PTT. This dual approach, which combines photothermal therapy and chemotherapy, enhances treatment precision and pathological site-specific accumulation, presenting strong potential for clinical translation.