Kolawole Olorunsola Praise, Pramanik Avijit, Kasani-Akula Pragathi, Rai Shivangee, Janorkar Sanika, Edorodion Zoe, Gates Kaelin, Kundu Sanchita, Ray Paresh Chandra
Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi 39217, United States.
ACS Appl Bio Mater. 2025 Jul 21;8(7):5959-5969. doi: 10.1021/acsabm.5c00592. Epub 2025 Jun 17.
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 (CoFeO) 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.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌，死亡率较高，这是由于缺乏靶向治疗以及对化疗和免疫治疗产生耐药性。由于泛素羧基末端水解酶L1（UCH-L1）（+）外泌体促进化疗耐药性，而程序性细胞死亡配体1（PD-L1）（+）外泌体在免疫治疗耐药中起关键作用，临床上迫切需要探索从血液中快速分析UCH-L1（+）和PD-L1（+）外泌体的策略，以预测化疗和免疫治疗的效果。在此，我们开发了一种多功能纳米平台，该平台使用与钴铁氧体（CoFeO）磁性纳米颗粒相连的抗体偶联的绿色和红色发光碳量子点，用于高精度分析TNBC来源的UCH-L1（+）和PD-L1（+）外泌体。具体而言，通过采用多种显微镜、光谱和超导量子干涉仪磁强计技术，我们表明该多功能纳米平台具有良好的化学稳定性、高光稳定性、强光致发光量子产率、优异的超顺磁行为和生物相容性。此外，通过利用策略性设计的附着抗UCH-L1抗体的红色发光（660 nm）磁性纳米平台和附着抗PD-L1抗体的绿色发光（530 nm）磁性纳米平台，报告的数据表明该多功能纳米平台能够从受感染的全血样本中选择性捕获和筛选约100%的UCH-L1（+）和PD-L1（+）外泌体。此外，我们展示了从全血中同时筛选UCH-L1（+）和PD-L1（+）外泌体的潜在应用，这表明该纳米平台可用于监测癌症的化疗和免疫治疗耐药性。
