Biomarker discovery and its clinical use have attracted considerable attention since early cancer diagnosis can significantly decrease mortality. Cancer biomarkers include a wide range of biomolecules, such as nucleic acids, proteins, metabolites, sugars, and cytogenetic substances present in human biofluids. Except for free-circulating biomarkers, tumor-extracellular vesicles (tEVs) and circulating tumor cells (CTCs) can serve as biomarkers for the diagnosis and prognosis of various cancers. Considering the potential of tumor biomarkers in clinical settings, several bioinspired detection systems based on nanotechnologies are in the spotlight for detection. However, tremendous challenges remain in detection because of massive contamination, unstable signal-to-noise ratios due to heterogeneity, nonspecific bindings, or a lack of efficient amplification. To date, many approaches are under development to improve the sensitivity and specificity of tumor biomarker isolation and detection. Particularly, the exploration of natural materials in biological frames has encouraged researchers to develop new bioinspired and biomimetic nanostructures, which can mimic the natural processes to facilitate biomarker capture and detection in clinical settings. These platforms have substantial influence in biomedical applications, owing to their capture ability, significant contrast increase, high sensitivity, and specificity. In this review, we first describe the potential of tumor biomarkers in a liquid biopsy and then provide an overview of the progress of biomimetic nanostructure platforms to isolate and detect tumor biomarkers, including in vitro and in vivo studies. Capture efficiency, scale, amplification, sensitivity, and specificity are the criteria that will be further discussed for evaluating the capability of platforms. Bioinspired and biomimetic systems appear to have a bright future to settle obstacles encountered in tumor biomarker detection, thus enhancing effective cancer diagnosis.

Liquid biopsy has the great potential of detecting early diseases before deterioration and is valued for screening abnormalities at early stage. In oncology, circulating DNA derived from shed cancer cells reflects the tissue of origin, so it could be used to locate tissue sites during early screening. However, the heterogenous parameters of different types limit the clinical application, making it inaccessible to encompass all the cancer types. Instead, for reproducible scenario as pregnancy, fetal cell-free DNA has been well utilized for screening aneuploidies. Noninvasive and convenient as is, it would be of great value in the next decades far more than early diagnosis. This review recapitulates the discovery and development of tumor and fetal cell-free DNA. The common factors are also present that could be taken into consideration when collecting, transporting, and preserving samples. Meanwhile, several protocols used for purifying cell-free DNA, either classic ones or through commercial kits, are compared carefully. In addition, the development of technologies for analyzing cell-free DNA have been summarized and discussed in detail, especially some up-todate approaches. At the end, the potential prospect of circulating DNA is bravely depicted. In summary, although there would be a lot of efforts before it's prevalent, cell-free DNA remains a promising tool in point-of-care diagnostic medicine.