Photoacoustic-imaging-guided therapy of functionalized melanin nanoparticles: combination of photothermal ablation and gene therapy against laryngeal squamous cell carcinomaElectronic supplementary information (ESI) available: FT-IR spectra of MNP, PLL and MNP-PLL (Fig. S1). UV-vis-NIR spectra of MNP-PLL (Fig. S2). Accumulative miRNA releases from MP-miRNA triggered by NIR irradiation for different times and at various power density (Fig. S3). The photothermal stability of MNP-PLL (Fig. S4). The

Multimodality therapy under imaging-guidance is significant to improve the accuracy of cancer treatment. In this study, a photoacoustic imaging (PAI)-guided anticancer strategy based on poly- l -lysine functionalized melanin nanoparticles (MNP-PLL) was developed to treat laryngeal squamous cell carcinoma (LSCC). As a promising alternative to traditional therapies for LSCC, MNP-PLL/miRNA nanoparticles were combined with photothermal ablation against primary tumors and miR-145-5p mediated gene therapy for depleting the metastatic potential of tumor cells. Furthermore, taking advantage of the photoacoustic properties of melanin, PAI guided therapy could optimize the time point of NIR irradiation to maximize the efficacy of photothermal therapy (PTT). The in vitro and in vivo results proved that the combined treatments displayed the most significant tumor suppression compared with monotherapy. By integrating thermo-gene therapies into a theranostic nanoplatform, the MNP-PLL/miR-145-5p nanoparticles significantly suppressed the LSCC progression, indicating their great potential use for cancer therapy. A photoacoustic imaging-guided anticancer strategy was developed based on poly- l -lysine functionalized melanin nanoparticles by integrating thermo-gene therapies.