Gold Nanobipyramids for Near-Infrared Fluorescence-Enhanced Imaging and Treatment of Triple-Negative Breast Cancer

SIMPLE SUMMARY: Gold nanoparticles have gained significant attention in the field of cancer research and treatment due to their unique properties and potential applications to medical imaging, targeted drug delivery, and combined use for cancer diagnosis and therapy. In this study, we developed novel gold nanoparticles with a bipyramidal shape, which have been functionalized to improve fluorescence imaging in the near-infrared biological window and facilitate the targeted delivery of chemotherapy to triple-negative breast tumors. We successfully tested these nanoparticle formulations in both in vitro and preclinical tumor models. Their ability to be combined with a wide range of fluorophores, therapeutics, and targeting agents demonstrates their clinical potential against various cancer types. ABSTRACT: There is an imminent need for novel strategies for the diagnosis and treatment of aggressive triple-negative breast cancer (TNBC). Cell-targeted multifunctional nanomaterials hold great potential, as they can combine precise early-stage diagnosis with local therapeutic delivery to specific cell types. In this study, we used mesoporous silica (MS)-coated gold nanobipyramids (MS-AuNBPs) for fluorescence imaging in the near-infrared (NIR) biological window, along with targeted TNBC treatment. Our MS-AuNBPs, acting partly as light amplification components, allow considerable metal-enhanced fluorescence for a NIR dye conjugated to their surfaces compared to the free dye. Fluorescence analysis confirms a significant increase in the dye’s modified quantum yield, indicating that MS-AuNBPs can considerably increase the brightness of low-quantum-yield NIR dyes. Meanwhile, we tested the chemotherapeutic efficacy of MS-AuNBPs in TNBC following the loading of doxorubicin within the MS pores and functionalization to target folate receptor alpha (FRα)-positive cells. We show that functionalized particles target FRα-positive cells with significant specificity and have a higher potency than free doxorubicin. Finally, we demonstrate that FRα-targeted particles induce stronger antitumor effects and prolong overall survival compared to the clinically applied non-targeted nanotherapy, Doxil. Together with their excellent biocompatibility measured in vitro, this study shows that MS-AuNBPs are promising tools to detect and treat TNBCs.