Hydrogel Microneedles Extracting Exosomes for Early Detection of Colorectal Cancer

Abstract

There are several methods for early diagnosis of tumors, such as detecting circulating tumor DNAs, detecting circulating tumor cells, or imaging with tumor-targeting contrast agents. However, these assays are time-consuming and may cause patient discomfort during the biopsy collecting process. Here, we develop a facile method for early diagnosis of tumors by extracting exosomes from interstitial fluid (ISF) using hydrogel microneedles (MNs). The hydrogel MNs expand in the skin to absorb the ISF, and the tumor exosomes contained in the ISF bind with the glypican-1 antibodies inside the hydrogel of MNs. After removing the hydrogel on the MNs, exosomes are separately purified from the ISF to analyze tumor-related biomarkers. Finally, colorectal cancer can be diagnosed by ELISA for the colorectal cancerinduced model mice. This noninvasive hydrogel MN system to obtain the exosome samples would play an important role in early cancer diagnosis.

Research Progress of Extracellular Vesicles-Loaded Microneedle Technology

“…Currently, the extraction of EVs from ISF using MNs is widespread [ 35 , 37 , 203 ]. MNs obtain EVs by researching the skin of colorectal cancer-induced model mice and patient-derived xenograft models of melanoma, thereby facilitating the early detection of melanoma and colorectal cancer and providing a novel liquid biopsy method with both diagnostic and prognostic value [ 35 , 204 ]. In a notable study, researchers utilized MNs functionalized with anti-CD63 antibodies to co-culture with astrocyte-derived EV suspension and capture CD63 + EV subpopulations [ 136 ].…”

“…Thus, the availability of MNs for delivery has also been proposed as a relatively alternative method [ 31 ]. Researchers have recently explored a range of applications utilizing MNs for the delivery of EVs to intradermal or other non-cutaneous tissues, as well as employing MNs for the detection of EVs in specific bodily or interstitial fluids [ 32 , 33 , 34 , 35 , 36 ]. These advancements underscore the considerable potential of MN-mediated EVs in therapeutic and diagnostic applications for prognostic purposes in clinical settings [ 37 ].…”

Microfluidic Chips Fabrication and Integration for Tumor‐Derived Exosomes Detection

“…Park et al used PDMS as a negative model to fabricate micron-sized polycaprolactone (PCL) hydrogel microneedle patches and modified them with antibodies overexpressing GPC-1 on the surface of exosomal membranes to specifically capture exosomes (Hydrogel Microneedles Extracting Exosomes for Early Detection of Colorectal Cancer). [68] The patch was inserted into the epithelial layer and exosomes were then captured, and with it dissolved, the patch was removed and transferred into PBS to collect exosomes for quantitative detection by ELISA, which was expected to achieve early diagnosis of colorectal cancer.…”

Microneedle systems: cell, exosome, and nucleic acid based strategies

“…Hydrogel MNs can be used not only for blood glucose detection but also for the detection of proteins, exosomes, and other substances when combined with probes, enabling in situ detection of biological indicators. 41,42 The wide variety of hydrogel materials available allows for the development of MNs with a high potential for expansion and innovation. For example, chitosan, a hydrogel material, exhibits inherent antibacterial and hemostatic properties, which can enhance the functionality of MNs.…”