Geometric chirality in inorganic nanostructures enables handedness- and polarization-enhanced photothermal tumor therapy in vivo

Chiral inorganic nanostructures with pronounced chiroptical activity are increasingly utilized across various scientific fields, yet understanding their direct impact on biological systems remains a complex challenge. In this study, we explore the effects of structural chirality on tumor photothermal therapy (PTT) using intrinsically chiral-shaped gold nanoparticles, highlighting their nanoscale geometric effects in vitro and in vivo. We demonstrate that the geometric chirality of these nanoparticles facilitates selective cellular uptake, with left-handed nanoparticles exhibiting a 1.5-fold higher uptake than their right-handed counterparts, indicating a preferential interaction with tumor cells. Furthermore, exposure to circularly polarized light (CPL) during PTT significantly amplifies the therapeutic effects. This enhancement is particularly pronounced when the helicity of CPL matches the handedness of nanoparticles, with left-handed nanoparticles under left-handed CPL achieving a cell kill rate three-fold higher than those under right-handed CPL. Such alignment also results in a significant reduction in axillary tumor volume in nude mice within two weeks. This work not only highlights the potential of stable, nanoscale chirality as highly efficient PTT agents but also provides crucial insights into chiral-dependent phenomenon in biosystems, paving the way for advanced biomedical applications.