Finding a needle in a haystack: A new technology is demonstrated to enrich circulating tumor cells (CTCs) with high efficiency by integrating an antibody‐coated silicon nanopillar (SiNP, see picture; gray) substrate with an overlaid polydimethylsiloxane (PDMS) microfluidic chaotic mixer (turquoise). It shows significantly improved sensitivity in detecting rare CTCs from whole blood, thus providing an alternative for monitoring cancer progression.
In the past decade, nanomedicine with its promise of improved therapy and diagnostics has revolutionized conventional health care and medical technology. Dendrimers and dendrimer-based therapeutics are outstanding candidates in this exciting field as more and more biological systems have benefited from these starburst molecules. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumour via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Imaging agents including MRI contrast agents, radionuclide probes, computed tomography contrast agents, and fluorescent dyes are combined with the multifunctional nanomedicine for targeted therapy with simultaneous cancer diagnosis. However, an important question reported with dendrimer-based therapeutics as well as other nanomedicines to date is the long-term viability and biocompatibility of the nanotherapeutics. This critical review focuses on the design of biocompatible dendrimers for cancer diagnosis and therapy. The biocompatibility aspects of dendrimers such as nanotoxicity, long-term circulation, and degradation are discussed. The construction of novel dendrimers with biocompatible components, and the surface modification of commercially available dendrimers by PEGylation, acetylation, glycosylation, and amino acid functionalization have been proposed as available strategies to solve the safety problem of dendrimer-based nanotherapeutics. Also, exciting opportunities and challenges on the development of dendrimer-based nanoplatforms for targeted cancer diagnosis and therapy are reviewed (404 references).
A nanostructured platform that combines electrospun TiO(2) nanofibers (TiNFs)-deposited substrate and cell-capture agent realizes significant capture of circulating tumor cells (CTCs). The enhanced local topographic interactions between the horizontally packed TiNFs deposited substrates and extracellular matrix scaffolds, in addition to anti-EpCAM/EpCAM biological recognition, contributes to the significantly enhanced capture efficiency compared to flat surfaces.
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.
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.
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.
Early diagnosis of colon cancer (CC) is clinically important, as it can significantly improve patients' survival rate and quality of life. Although the potential role for small extracellular vesicles (sEVs) in early detection of many diseases has been repeatedly mentioned, systematic screening of plasma sEVs derived early CC specific biomarkers has not yet been reported. In this work, plasma sEVs enriched fractions were derived from 15 early-stage (TisN0M0) CC patients and 10 normal controls (NC). RNA sequencing identified a total number of 95 sEVs enriched fraction derived miRNAs with differential expression between CC and NC, most of which (60/95) was in well accordance with tissue results in the Cancer Genome Atlas (TCGA) dataset. Among those miRNAs, we selected let-7b-3p, miR-139-3p, miR-145-3p, and miR-150-3p for further validation in an independent cohort consisting of 134 participants (58 CC and 76 NC). In the validation cohort, the AUC of 4 individual miRNAs ranged from 0.680 to 0.792. A logistic model combining two miRNAs (i.e. let-7b-3p and miR-145-3p) achieved an AUC of 0.901. Adding the 3rd miRNA into this model can further increase the AUC to 0.927. Side by side comparison revealed that sEVs miRNA profile outperformed cell-free plasma miRNA in the diagnosis of early CC. In conclusion, we suggested that circulating sEVs enriched fractions have a distinct miRNA profile in CC patients, and sEVs derived miRNA could be used as a promising biomarker to detect CC at an early stage.
Handpick single cancer cells: A modified NanoVelcro Chip is coupled with ArcturusXT laser capture microdissection (LCM) technology to enable the detection and isolation of single circulating tumor cells (CTCs) from patients with prostate cancer (PC). This new approach paves the way for conducting next‐generation sequencing (NGS) on single CTCs.
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