Actively Targeted Deep Tissue Imaging and Photothermal-Chemo Therapy of Breast Cancer by Antibody-Functionalized Drug-Loaded X-Ray-Responsive Bismuth Sulfide@Mesoporous Silica Core-Shell Nanoparticles.

ABSTRACT

A theranostic platform combining synergistic therapy and real-time imaging attracts enormous attention but still faces great challenges, such as tedious modifications and lack of efficient accumulation in tumor. Here, a novel type of theranostic agent, bismuth sulfide@mesoporous silica (Bi2S3@ mPS) core-shell nanoparticles (NPs), for targeted image-guided therapy of human epidermal growth factor receptor-2 (HER-2) positive breast cancer is developed. To generate such NPs, polyvinylpyrrolidone decorated rod-like Bi2S3 NPs are chemically encapsulated with a mesoporous silica (mPS) layer and loaded with an anticancer drug, doxorubicin. The resultant NPs are then chemically conjugated with trastuzumab (Tam, a monoclonal antibody targeting HER-2 overexpressed breast cancer cells) to form Tam-Bi2S3@mPS NPs. By in vitro and in vivo studies, it is demonstrated that the Tam-Bi2S3@mPS bear multiple desired features for cancer theranostics, including good biocompatibility and drug loading ability as well as precise and active tumor targeting and accumulation (with a bismuth content in tumor being ≈16 times that of nontargeted group). They can simultaneously serve both as an excellent contrast enhancement probe (due to the presence of strong X-ray-attenuating bismuth element) for computed tomography deep tissue tumor imaging and as a therapeutic agent to destruct tumors and prevent metastasis by synergistic photothermalchemo therapy.