We engineered a new, targeted multifunctional nanostructure that combines Near-Infrared (NIR) metal enhanced fluorescence imaging of triple negative breast cancer cells with local chemotherapeutic drug delivery. This nanostructure consisted of: (i) a plasmonic gold Au nanobipyramids (AuNBP) core that acts as a light amplification component for NIR dyes, (ii) a mesoporous silica (MS) coating around the AuNBPs, serving as a spacer of controlled distance between the AuNBPs and the NIR fluorescent dyes, which is a prerequisite for large fluorescence enhancement. Meanwhile, this MS layer, containing several channel-like nanopores, allows our nanostructures to serve as anticancer-drug carriers, (iii) a surface labelling of the MS layer with the NIR fluorophore DyLight™ 800 (DL800), to investigate its fluorescence enhancement by the AuNBP core, and potential in triple negative breast cancer cell imaging, and (iv) a surface functionalization of the nanostructures with folic acid (FA) for FRα targeting. We showed that dye conjugation to the AuNBPs allows considerable fluorescence enhancement of around 14 times compared to the free dye. Using time-resolved photoluminescence measurements, we also demonstrated a significant increase in the modified quantum yield for DL800 bound to AuNBPs, which illustrates that these particles can considerably increase the brightness of low-quantum-yield NIR dyes and therefore improve their possible performance in clinical applications. In the absence of drug loading, our nanostructures presented excellent biocompatibility in vitro, indicating their suitability for such applications. Furthermore, in vitro fluorescence imaging and viability measurements, showed that FA-functionalized, doxorubicin-loaded particles target FRα-positive cells with significant specificity and reduced their viability more than free doxorubicin. Finally, using preclinical murine tumor models, we illustrated that our FRα targeted particles induce antitumor effects and prolong overall survival in animals, to a higher degree than a clinically applied non-targeted nanomedicine (Doxil).
The results of the project highlighted the potential clinical utility of our targeted multifunctional nanostructure for concomitant imaging/detection and treatment of breast cancer. Furthermore, the high flexibility of our nanostructure to several therapeutic modalities and targeting agents allows for modifications to improve further its potency and efficacy. For instance, in parallel to localized drug delivery, the AuNBP core of our nanostructures could also be used as a photothermal therapy mediator for multimodal treatment of aggressive subtypes of breast cancers. Therefore, further development and clinical testing of the proposed nanostructures could have the potential to lead to improved cancer detection and therapy.
