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Multifunctional Nanoplatform for Highly Accurate Profiling of Triple-Negative Breast Cancer-Derived Chemo- and
Olorunsola Praise Kolawole1, Avijit Pramanik1, Pragathi Kasani-Akula1
1Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi 39217, United States.
Abstract:
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.
Insights
Researchers developed a novel nanoplatform for rapid blood profiling of exosomes, aiding in predicting triple-negative breast cancer treatment outcomes. This technology helps identify resistance to chemotherapy and immunotherapy by detecting specific exosome markers.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents high mortality due to limited targeted therapies and resistance to existing treatments.
- Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) and programmed cell death ligand-1 (PD-L1) positive exosomes are implicated in chemo- and immunotherapy resistance, respectively.
- Accurate and rapid profiling of these exosomes in blood is crucial for predicting treatment efficacy.
Purpose of the Study:
- To develop a multifunctional nanoplatform for simultaneous detection of UCH-L1 and PD-L1 positive exosomes in blood.
- To assess the nanoplatform's efficiency in capturing and screening exosomes from whole blood samples.
- To evaluate the potential of this platform for monitoring treatment resistance in TNBC.
Main Methods:
- Fabrication of a nanoplatform using antibody-conjugated carbon quantum dots and cobalt ferrite magnetic nanoparticles.
- Utilizing antibody-conjugated magnetic nanoplatforms with distinct luminescence (red for UCH-L1, green for PD-L1).
- Employing various microscopic, spectroscopic, and magnetic techniques to characterize the nanoplatform and its performance.
Main Results:
- The nanoplatform demonstrated excellent chemical stability, photostability, luminescence, superparamagnetism, and biocompatibility.
- The system achieved selective capture and screening of approximately 100% of UCH-L1 and PD-L1 positive exosomes from whole blood.
- Simultaneous screening of both exosome types was successfully showcased, indicating potential for resistance monitoring.
Conclusions:
- The developed multifunctional nanoplatform enables highly accurate and rapid profiling of TNBC-derived exosomes.
- This technology holds significant promise for predicting chemo- and immunotherapy response in TNBC patients.
- The platform offers a potential tool for real-time monitoring of cancer treatment resistance.
