Multifunctional Nanoplatform for Highly Accurate Profiling of Triple-Negative Breast Cancer-Derived Chemo- and Immunotherapy Resistance Exosomes

Triple-negative breast cancer (TNBC) is the most malignant breast cancer with a higher mortality rate, which is due to the lack of targeted therapies and the development of resistance to chemotherapy and immunotherapy. Since the ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) (+) exosome promotes chemoresistance and the programmed cell death ligand-1 (PD-L1) (+) exosome plays a crucial role in immunotherapy resistance, there is an urgent need in clinics to explore strategies for the rapid profiling of UCH-L1(+) and PD-L1(+) exosomes from blood to predict chemo- and immunotherapy treatment outcomes. Herein, we develop a multifunctional nanoplatform using antibody-conjugated green- and red-emissive carbon quantum dots attached to cobalt ferrite (CoFe₂O₄) magnetic nanoparticles for the highly accurate profiling of TNBC-derived UCH-L1(+) and PD-L1(+) exosomes. Specifically, by employing multiple microscopic, spectroscopic, and SQUID magnetometer techniques, we show that the multifunctional nanoplatform exhibits good chemical stability, high photostability, strong photoluminescence quantum yield, excellent superparamagnetic behavior, and biocompatibility. Moreover, by leveraging strategically designed anti-UCH-L1 antibody-attached red luminescence (660 nm) magnetic nanoplatform and anti-PD-L1 antibody-attached green luminescence (530 nm) magnetic nanoplatform, the reported data demonstrate that the multifunctional nanoplatform has the capability for capturing and screening ∼100% UCH-L1(+) and PD-L1(+) exosomes selectively from infected whole-blood samples. Furthermore, we showcase the potential application for the screening of UCH-L1 (+) and PD-L1(+) exosomes simultaneously from whole blood, which indicates that the nanoplatform may be used for monitoring chemotherapeutic and immunotherapeutic resistance of cancer.