Multiple cell death pathways triggered by temperature-mediated synergistic effect derived from chiral phototheranostic ablation nanoagents

Abstract Inorganic nanomaterials equipped with photosensitive chirality are well-expected as panaceas for many biological issues such as Parkinson's disease, DNA cleavage and cancer therapy owing to their versatile physical and chemical properties. Herein, we employ small size chiral MoO3-x nanodots capped with amino acid (cysteine) as chirality-dependent contrast agents/ photosensitizers for in vivo photoacoustic imaging guided photothermal therapy. Due to the enhanced incident-light-selective absorption at near-infrared (NIR) region and rapid body clearance capability, chiral MoO3-x show complete tumor ablation within 10 days without apparent in vivo toxicity when enantiomerically irradiated with corresponding circularly polarized NIR laser. More importantly, due to the mild temperature photothermal treatment, such chiral nanosystems exhibit a delayed cell apoptosis effect which is confirmed by the apoptosis related gene expression and immunofluorescence analysis in both intrinsic and extrinsic pathways unveiling new insights on synergistic relations between photothermal effects and gene expressions. This concept of inorganic theranostic nanoagent qualified with short photo-irradiation time for photothermal therapy and spontaneous cell apoptosis provides an efficient and biologically safe cancer treatment approach which integrates the advances of chiroptics and photo-gene related therapy strategies.