Matrix metallopeptidase 2 targeted delivery of gold nanostars decorated with IR-780 iodide for dual-modal imaging and enhanced photothermal/photodynamic therapy

Abstract Nanotheranostics has gained increasing interest, as it offers a great potential to realize personalized diagnostics and therapy. In this work, we report a facile approach of the fabrication of gold nanostars (GNS) attached with matrix metalloproteinases (MMP2) polypeptides (Ac-GPLGIAGQ) and IR-780 iodide through bovine serum albumin (BSA) for targeted dual-modal photoacoustic (PA)/near-infrared (NIR) fluorescence imaging and enhanced photothermal therapy (PTT)/photodynamic therapy (PDT) for lung cancer. MMP2 polypeptides served as the targeting ligand, IR-780 iodide functioned as the NIR fluorescence imaging agent as well as PTT/PDT agent, and GNS acted as the carrier of IR-780 molecules and performed PA imaging and PTT. DLS and CCK-8 assay demonstrated that the nanoprobes (GNS@BSA/I-MMP2) exhibited excellent stability and biocompatibility under physiological conditions. Subsequent in vitro studies verified that GNS@BSA/I-MMP2 nanoparticles (NPs) were effectively internalized by A549 cancer cells and exhibited remarkable antitumor efficacy. Furthermore, GNS@BSA/I-MMP2 NPs could specifically target the tumor and significantly suppress the tumor growth, and their antitumor effects were mainly through the synergistic effects of PDT and PTT based on IR-780 and GNS. These findings imply the potential of GNS@BSA/I-MMP2 NPs as a targeting PA/NIR probe in tumor diagnosis and combined therapy with a single light source. Statement of Significance We reported a convenient and facile approach to load IR-780 iodides in gold nanostars (GNS). This material could simultaneously perform near-infrared imaging/photoacoustic imaging and thermotherapy/photodynamic therapy. MMP2 coating on the surface of GNS@BSA/IR-780 promoted the prepared nanoparticles (GNS@BSA/I-MMP2) to target the tumor region. The heat generated by the synergistic effect of the GNS and IR-780 molecules resulted in the high temperature of the GNS@BSA/I-MMP2 NPs, which efficiently suppressed the growth of tumor, and the tumor volume decreased by 93% compared with that in the PBS groups with laser irradiation.