Within cancer, there is a large wealth of diversity, complexity, and information that nature has engineered rendering it challenging to identify reliable detection methods. Therefore, the development of simple and effective techniques to delineate the fine characteristics of cancer cells can have great potential impacts on cancer diagnosis and treatment. Herein, we report a magnetic glyco-nanoparticle (MGNP) based nanosensor system bearing carbohydrates as the ligands, not only to detect and differentiate cancer cells but also to quantitatively profile their carbohydrate binding abilities by magnetic resonance imaging (MRI). Using an array of MGNPs, a range of cells including closely related isogenic tumor cells, cells with different metastatic potential and malignant vs normal cells can be readily distinguished based on their respective "MRI signatures". Furthermore, the information obtained from such studies helped guide the establishment of strongly binding MGNPs as antiadhesive agents against tumors. As the interactions between glyco-conjugates and endogenous lectins present on cancer cell surface are crucial for cancer development and metastasis, the ability to characterize and unlock the glyco-code of individual cell lines can facilitate both the understanding of the roles of carbohydrates as well as the expansion of diagnostic and therapeutic tools for cancer.
Exosomes, which are membranous nanovesicles, are actively released by cells and have been attributed to roles in cell-cell communication, cancer metastasis, and early disease diagnostics. The small size (30–100 nm) along with low refractive index contrast of exosomes makes direct characterization and phenotypical classification very difficult. In this work we present a method based on Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows multiplexed phenotyping and digital counting of various populations of individual exosomes (>50 nm) captured on a microarray-based solid phase chip. We demonstrate these characterization concepts using purified exosomes from a HEK 293 cell culture. As a demonstration of clinical utility, we characterize exosomes directly from human cerebrospinal fluid (hCSF). Our interferometric imaging method could capture, from a very small hCSF volume (20 uL), nanoparticles that have a size compatible with exosomes, using antibodies directed against tetraspanins. With this unprecedented capability, we foresee revolutionary implications in the clinical field with improvements in diagnosis and stratification of patients affected by different disorders.
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