Circulating rare cells in the blood are of great significance for both materials research and clinical applications. For example, circulating tumor cells (CTCs) have been demonstrated as useful ...biomarkers for “liquid biopsy” of the tumor. Circulating fetal nucleated cells (CFNCs) have shown potential in noninvasive prenatal diagnostics. However, it is technically challenging to detect and isolate circulating rare cells due to their extremely low abundance compared to hematologic cells. Nanostructured substrates offer a unique solution to address these challenges by providing local topographic interactions to strengthen cell adhesion and large surface areas for grafting capture agents, resulting in improved cell capture efficiency, purity, sensitivity, and reproducibility. In addition, rare‐cell retrieval strategies, including stimulus‐responsiveness and additive reagent‐triggered release on different nanostructured substrates, allow for on‐demand retrieval of the captured CTCs/CFNCs with high cell viability and molecular integrity. Several nanostructured substrate‐enabled CTC/CFNC assays are observed maturing from enumeration and subclassification to molecular analyses. These can one day become powerful tools in disease diagnosis, prognostic prediction, and dynamic monitoring of therapeutic response—paving the way for personalized medical care.
Circulating rare cells are of great significance as a surrogate tissue source for implementing noninvasive diagnoses. Recent progress in exploring the use of nanostructured substrates for detecting and characterizing circulating tumor cells and circulating fetal nucleated cells is reviewed. Different nanostructures, cell retrieval strategies, enumeration, morphological, and molecular analysis in clinical applications, and future perspectives are comprehensively discussed.
Hepatocellular carcinoma (HCC) is among the leading causes of worldwide cancer‐related morbidity and mortality. Poor prognosis of HCC is attributed primarily to tumor presentation at an advanced ...stage when there is no effective treatment to achieve the long term survival of patients. Currently available tests such as alpha‐fetoprotein have limited accuracy as a diagnostic or prognostic biomarker for HCC. Liver biopsy provides tissue that can reveal tumor biology but it is not used routinely due to its invasiveness and risk of tumor seeding, especially in early‐stage patients. Liver biopsy is also limited in revealing comprehensive tumor biology due to intratumoral heterogeneity. There is a clear need for new biomarkers to improve HCC detection, prognostication, prediction of treatment response, and disease monitoring with treatment. Liquid biopsy could be an effective method of early detection and management of HCC. Circulating tumor cells (CTCs) are cancer cells in circulation derived from the original tumor or metastatic foci, and their measurement by liquid biopsy represents a great potential in facilitating the implementation of precision medicine in patients with HCC. CTCs can be detected by a simple peripheral blood draw and potentially show global features of tumor characteristics. Various CTC detection platforms using immunoaffinity and biophysical properties have been developed to identify and capture CTCs with high efficiency. Quantitative abundance of CTCs, as well as biological characteristics and genomic heterogeneity among the CTCs, can predict disease prognosis and response to therapy in patients with HCC. This review article will discuss the currently available technologies for CTC detection and isolation, their utility in the clinical management of HCC patients, their limitations, and future directions of research.
A platform for capture and release of circulating tumor cells (CTCs) is demonstrated by utilizing aptamer grafted silicon nanowires. Here, single‐stranded DNA‐aptamers are generated via the ...Cell‐SELEX process to serve as capture agents, allowing specific capture and release of non‐small cell lung cancer (NSCLC) CTCs from whole‐blood samples with minimum contamination and negligible disruption to CTC viability and functions.
Background and Aims
Hepatocellular carcinoma (HCC) remains a leading cause of cancer‐related mortality, with a disproportionate impact on racial/ethnic minority groups. However, state‐level variation ...in racial/ethnic disparities and temporal trends of HCC incidence remain unknown. Therefore, we aimed to characterize (1) state‐level racial/ethnic disparity in HCC incidence, (2) state‐level temporal changes in HCC incidence, and (3) the ecological correlation between HCC incidence and obesity/physical activity levels in the USA.
Approach and Results
Trends in HCC incidence between 2001 and 2017 were calculated using data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and End Results, and annual percent change in rates were calculated. State‐level percent of obesity and level of physical activity were obtained from the Centers for Disease Control and Prevention, and the correlation among obesity, physical activity, and state‐specific average annual percent change was tested by Pearson correlation coefficient. There were striking state‐level racial/ethnic disparities in HCC incidence; incidence rate ratios ranged between 6.3 and 0.9 in Blacks, 6.1 and 1.7 in Asians/Pacific Islanders, 3.8 and 0.9 in Hispanics, and 6.0 and 0.9 in American Indians/Alaska Natives (compared with Whites as reference). Despite overall decreasing HCC incidence rates after 2015, HCC incidence continued increasing in 26 states over recent years. HCC incidence trends had a moderate correlation with state‐level obesity (r = 0.45, P < 0.001) and a moderate inverse correlation with state‐level physical activity (r = −0.40, P = 0.004).
Conclusions
There is wide state‐level variation in racial/ethnic disparity of HCC incidence. There are also disparate incidence trends across states, with HCC incidence continuing to increase in over half of the states. Regional obesity and lack of physical activity have moderate correlations with HCC incidence trends, suggesting that interventions targeting these factors may help curb rising HCC incidence.
A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires. In this platform, integration of ligand‐receptor recognition, ...nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells. Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.
Collecting circulating tumor cells (CTCs) shed from solid tumor through a minimally invasive approach provides an opportunity to solve a long‐standing oncology problem, the real‐time monitoring of ...tumor state and analysis of tumor heterogeneity. However, efficient capture and detection of CTCs with diverse phenotypes is still challenging. In this work, a microfluidic assay is developed using the rationally‐designed aptamer cocktails with synergistic effect. Enhanced and differential capture of CTCs for nonsmall cell lung cancer (NSCLC) patients is achieved. It is also demonstrated that the overall consideration of CTC counts obtained by multiple aptamer combinations can provide more comprehensive information in treatment monitoring.
Aptamer cocktails with a synergistic effect are obtained through a rational design. In the combined use of a silicon nanowire substrate embedded microfluidic chip, the enhanced and differential capture of circulating tumor cells (CTCs) is realized for nonsmall cell lung cancer patients. The potential of this assay in the characterization of CTC heterogeneity is discussed.
Confined to one cell: A method to detect and isolate single circulating melanoma cells (CMCs; see figure) has been produced by integrating a polymer‐nanofiber‐embedded nanovelcro cell‐affinity assay ...with a laser microdissection (LMD) technique. This method is able to separate CMCs from normal white blood cells (WBCs) and sequence individual cells for a specific mutation related to cancer progression, allowing for more personalized cancer therapy.
An efficient nonviral platform for high-throughput and subcellular precision targeted intracellular delivery of nucleic acids in cell culture based on magnetic nanospears is reported. These magnetic ...nanospears are made of Au/Ni/Si (∼5 μm in length with tip diameters <50 nm) and fabricated by nanosphere lithography and metal deposition. A magnet is used to direct the mechanical motion of a single nanospear, enabling precise control of position and three-dimensional rotation. These nanospears were further functionalized with enhanced green fluorescent protein (eGFP)-expression plasmids via a layer-by-layer approach before release from the underlying silicon substrate. Plasmid functionalized nanospears are guided magnetically to approach target adherent U87 glioblastoma cells, penetrating the cell membrane to enable intracellular delivery of the plasmid cargo. After 24 h, the target cell expresses green fluorescence indicating successful transfection. This nanospear-mediated transfection is readily scalable for the simultaneous manipulation of multiple cells using a rotating magnet. Cell viability >90% and transfection rates >80% were achieved, which exceed conventional nonviral intracellular methods. This approach is compatible with good manufacturing practices, circumventing barriers to the translation and clinical deployment of emerging cellular therapies.
Nanostructured conducting polymer nanodots are prepared by electropolymerization of carboxylic acid group functionalized monomer in dichloromethane directly onto substrates. They demonstrate enhanced ...yields for the capture of tumor cells compared to smooth surfaces due to a synergistic effect of the capture agents and nanostructures.
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