Monitoring Clinical–Pathological Grading of Hepatocellular Carcinoma Using MicroRNA-Guided Semiconducting Polymer Dots

Abstract

MicroRNAs (miRNAs) are a class of small, noncoding RNAs involved in nearly all genetic central dogma processes and human biological behavior, which also play a significant role in the pathological activity of tumors, such as gene transcription, protein translation, and exosome secretion. Therefore, through the navigation of certain specific miRNAs, we can trace the specific physiological processes or image some specific tissues. Designing and accurately positioning microRNA (miRNA)-sensitive fluorescent nanoprobes with benign specificity and recognition in cells or tissues are a challenging research field. To solve the difficulties, we introduce four semiconducting polymer dots (Pdots) as nanoprobes linked by specific miRNA antisense sequences for monitoring the pathological grading by the variation in miRNA expression. Based on the base pairing principle, these miRNAsensitive Pdots could bind to specific miRNAs within the cancerous cells. As impacted by the background of different pathology gradings, the proportions of the four hepatocellular carcinoma (HCC)-specific miRNAs within the cancerous cell are different, and the pathological grading of the patient tissues can be determined by comparing the palette combinations. The short single-stranded RNA-functionalized Pdots, which have excellent microRNA sensitivity, are observed in an experimental cell model and a series of tissue specimens from HCC patients for the first time. Using the Forster (or fluorescence) resonance energy transfer (FRET) model of Pdots and Cy3dt tag to simulate in vivo miRNA detection, the superior sensitivity and specificity of these nanoprobes are verified. The interference of subjective factors in traditional single/bis-dye emission intensity detection is abandoned, and multiple label staining is used to enhance sensitivity further and reduce the false-positive rate. The feasibility exhibited by this novel staining method is verified in normal hepatocellular HCC cell lines and 16 frozen ultrathin tissue sections, which are employed to quantify pathological grading-related color presentation systems for clinical doctors and pathologists' use. The intelligently designed miRNAguided Pdots will emerge as an ideal platform with promising biological imaging.

Identification of the genetic central dogma in osteogenic differentiation of MSCs by osteoinductive medium from transcriptional data sets

“… 9 Detailly, the pathways such as DNA replication, Mismatch repair, Ribosome, Spliceosome, Aminoacyl‐tRNA biosynthesis, RNA transport, RNA degradation, and messenger RNA surveillance pathway are associated to GCD due to their participations in DNA–RNA–protein processes. 11 , 12 , 13 , 14 , 24 , 25 For example, the disfunction of ribosome and associated pathways, that is, the RNA transcription and protein translation, attributes to osteoarthritis. 14 In human cells, mechanical stress influences the rheology through the pathways related to DNA replication and repair.…”

“… 13 Thus, this central dogma is certainly work in organic species and participates in massive biological processes without doubt. 12 , 13 , 14 However, its certain roles in osteogenic differentiation have not been well described due to the limitation of technology for the past. Recently, the prosperous of high‐throughput technology open a new era for understanding the activities and functions of GCD in various biological processes 15 as well as its role in osteogenesis.…”

“…In human cells, mechanical stress influences the rheology through the pathways related to DNA replication and repair 13 . Thus, this central dogma is certainly work in organic species and participates in massive biological processes without doubt 12–14 . However, its certain roles in osteogenic differentiation have not been well described due to the limitation of technology for the past.…”

“… 9 To date, the concepts of splicing and ribonucleic acid (RNA) editing consummate the GCD; meanwhile, entire information on DNA–RNA–protein processes is included. 10 , 11 GCD makes different contributions to many physical and pathological processes, including oncogenesis, 12 mechanical stress on human cells, 13 osteoarthritis, 14 and so on. However, the roles of GCD in the differentiation of stem cells remain unknown.…”

Recent Advances in Interventional Fluorescence Imaging: Toward the Precise Visualization of Transarterial Mini-Invasive Delivery Systems

“…Hepatocellular carcinoma (HCC) is a very common cancer in the world and is seriously threatening public health. , Oncologic surgery is the first choice in the clinical treatment of HCC in removing minimal damage to healthy tissues. However, only a small proportion of HCC patients are suitable for direct resection.…”