Tumor Environment-Responsive Gold Nanodendrites for Nanoprobe-Based Single-Cell Raman Imaging and Tumor-Targeted Chemo-Photothermal Therapy

The utilization of nanodendrites (NDs) possessing densely branched properties and biomimetic architectures has exhibited great promise in tumor therapy owing to their extended in vivo circulation duration and exceptional photo-thermal efficiency. Nevertheless, traditional NDs are deficient in terms of specific surface modification and the ability to target tumors, thereby restricting their potential for wider clinical applications. To address the aforementioned limitations, we developed spherical coronavirus-like gold NDs using a seed-mediated approach. These nanoparticles have been coated with silk fibroin (SF) as a capping agent. Our results demonstrated that these NDs possess a favorable drug-loading capacity (~65.25%) and light-triggered release characteristics of doxorubicin hydrochloride (DOX). Moreover, specific probe-functionalized NDs exhibited exceptional surface-enhanced Raman scattering (SERS) characteristics, enabling high-sensitivity Raman imaging of unstained individual cells for an extended period (more than 24 h), as well as the real-time monitoring of endocytic NDs. Furthermore, ND@DOX conjugated with tumor-targeting peptides demonstrated minimal cytotoxicity and effective targeting towards cancer cells in vitro, as well as responsiveness to the tumor microenvironment in vivo. These properties led to the highest level of synergistic tumor-killing efficiency when stimulated by a near-infrared (NIR) laser excitation at 808 nm. Thus, the virus-like ND functionalized with SF presents a novel type of nanocarrier that exhibits significant potential for synergistic applications in precision medicine.