Multifunctional A7R Peptide-Modified Hollow Mesoporous Silica@Ag2S Nanotheranostics for Photoacoustic/Near-Infrared Fluorescence Imaging-Guided Tumor-Targeted Chemo-Photothermal Therapy

: The fabrication of theranostic nanoplatforms which combine diagnostic and therapeutic functions have become an emerging approach for personal nanomedicine. Herein, a multifunctional nanoplatform consisting of A7R peptide (ATWLPPR) conjugated hollow mesoporous silica nanoparticles decorated with Ag₂S nanodots (Ag₂S@HMSs-A7R) has been developed as an efficient theranostic agent for simultaneous photoacoustic (PA) imaging and near-infrared fluorescence imaging (NIRF)-guided targeted chemotherapy and photothermal therapy against human breast cancer MDA-MB-231 cells. The design of Ag₂S doped HMSs by in situ controlled growth of ultrasmall Ag₂S nanodots in the mesopores of HMSs. The synthesized multifunctional nanoplatform exhibits high doxorubicin (DOX) loading capability (451 mg/g) and can be precisely controlled by glutathione (GSH), acidic environment and external laser irradiation. Thanks to the strong tunable NIR absorbance of Ag₂S, the nanoplatform produce effective photoacoustic capacity and superb photothermal conversion under light irradiation, thereby exhibiting sufficient in vivo fluorescence and photoacoustic signals as well as desirable photothermal therapeutic performance. Importantly, A7R peptide can selectively bind the Neuropilin-1 (NRP-1) receptor which overexpressed by the MDA-MB-231 cells. The achieved Ag₂S@HMSs-A7R possess ideal imaging capability for both PA and NIRF imaging in vivo, and the anti-tumor effect of Ag₂S@HMSs(DOX)-A7R was studied in vitro and in vivo, showing remarkable synergistic chemo-photothermal effect (combination index, CI < 1). Over all, the strategy of utilizing triple-responsive nanocarriers presents a highly promising potential as an efficient method for cancer theranostics.