Fan Chunhai

A graphene oxide-based fluorescent biosensor for the analysis of peptide-receptor interactions and imaging in somatostatin receptor subtype 2 overexpressed tumor cells.

Analysis of peptide-receptor interactions provides insights for understanding functions of proteins in cells. In this work, we report the development of a fluorescent biosensor for the analysis of peptide-receptor interactions using graphene oxide (GO) and fluorescein isothiocyanate (FITC)-labeled octreotide (FOC). Octreotide is a synthesized cyclic peptide with somatostatin-like bioactivity that has been clinically employed. FOC exhibits high adsorption affinity for GO, and its binding results in efficient fluorescence quenching of FITC. Interestingly, the specific binding of the antibody anti-octreotide (AOC) with FOC competitively releases FOC from the GO surface, leading to the recovery of fluorescence. By using this GO-based fluorescent platform, we can detect AOC with a low detection limit of 2 ng/mL. As a step further, we employ this GO-FOC biosensor to image somatostatin receptor subtype 2 overexpressed AR42J tumor cells, which demonstrates high promise for molecular imaging in cancer diagnosis.

Nanoprobes for super-resolution fluorescence imaging at the nanoscale

Compared with other imaging techniques, fluorescence microscopy has become an essential tool to study cell biology due to its high compatibility with living cells. Owing to the resolution limit set by the diffraction of light, fluorescence microscopy could not resolve the nanostructures in the range of < 200 nm. Recently, many techniques have been emerged to overcome the diffraction barrier, providing nanometer spatial resolution. In the course of development, the progress in fluorescent probes has helped to promote the development of the high-resolution fluorescence nanoscopy. Here, we describe the contributions of the fluorescent probes to far-field super resolution imaging, focusing on concepts of the existing super-resolution nanoscopy based on the photophysics of fluorescent nanoprobes, like photoswitching, bleaching and blinking. Fluorescent probe technology is crucial in the design and implementation of super-resolution imaging methods.

Highly sensitive biosensors based on water-soluble conjugated polymers

Conjugated, conductive polymers are a kind of important organic macromolecules, which has found applications in a variety of areas. The application of conjugated polymers in developing fluorescent biosensors represents the merge of polymer sciences and biological sciences. Conjugated polymers are very good light harvesters as well as fluorescent polymers, and they are also “molecular wires”. Through elaborate designs, these important features, i.e. efficient light harvesting and electron/energy transfer, can be used as signal amplification in fluorescent biosensors. This might significantly improve the sensitivity of conjugated polymer-based biosensors. In this article, we reviewed the application of conjugated polymers, via either electron transfer or energy transfer, to detections of gene targets, antibodies or enzymes. We also reviewed recent efforts in conjugated polymer-based solid-state sensor designs as well as chip-based multiple target detection. Possible directions in this conjugated polymer-based biosensor area are also discussed.

Programmed self-assembly of DNA origami nanoblocks into anisotropic higher-order nanopatterns

Anisotropic nanopatterns have potentials in constructing novel plasmonic structures which have various applications in such as super-resolution microscopy, medicine, and sensors. However, it remains challenging to build big anisotropic nanopatterns that are suitable for big noble metal nanoparticles. Herein, we report a simple and reliable strategy for constructing DNA origami-based big anisotropic nanopatterns with controlled size and shape, nanoscale resolution, and fully addressability. Two kinds of basic DNA origami nanoblocks — cross-shaped and rectangular DNA origami units were used. We have demonstrated that by encoding nanoblocks’ edges, anisotropic higher-order nanopatterns, such as dimer, trimer, tetramer and mini “windmill” like pentamer nanopatterns could be constructed. To show the potential use as template to direct the assembly of anisotropic nanoparticles arrays, a proof of concept work was conducted by anchoring streptavidin nanoparticles on the “windmill” template to form a chiral array. Significantly, these nanopatterns have the sizes of hundreds of nanometers, which are in principle also suitable for big noble metal nanoparticles arrays.

Cytotoxicity of cadmium-based quantum dots

Semiconductor Quantum dots (QDs) have raised great attention because of their superior optical properties and wide utilization in biological and biomedical studies. More recently, there have been intense concerns on cytotoxicity assessment of QDs. Most QDs are made of heavy metal ions (e.g., Cd2+), which may result in potential in vitro toxicity that hampers their practical applications. In this article, we aim to summarize recent progress on mechanistic studies of cytotoxicity of II-IV QDs. We have studied the cytotoxicity of a series of aqueous synthesized QDs (aqQDs), i.e. CdTe, CdTe/CdS core-shell structured and CdTe/CdS/ZnS core-shell-shell structured aqQDs. Our results suggested that released cadmium ions are responsible for the observed cytotoxicity of cadmium-based QDs. The fact that CdTe/CdS/ZnS core-shell-shell structured QDs are nearly nontoxic to cells further confirmed the role of released cadmium ions on cytotoxicity, and the effective protection of the ZnS shell. However, intracellular level of Cd2+ ions cannot be the only reason since the comparison with CdCl2-treated cells suggests there are other factors contributed to the cytotoxicity of aqQDs. Our studies on genome-wide gene expression profiling and subcellular localization of aqQDs with synchrotron-based scanning transmission X-ray microscopy (STXM) further suggest that the cytotoxicity of CdTe QDs not only comes from the release of Cd2+ ions but also intracellular distribution of QD nanoparticles in cells and the associated nanoscale effects

DNA/RNA based logic gates and computing

DNA and RNA molecules possess precise recognition and powerful signal storage abilities. By exploiting their biological properties, it is possible to construct molecule-scale logic gates and realize logistic operations which, as an emerging multidisciplinary area between computer sciences and molecular biology, has intrigued great research attention. In this article, we summarize methods to construct logic gates by exploiting enzymatic and structural properties of DNA and RNA, and approaches to integrate logic gates into complex logistic operations. Finally, we introduce biomedical applications of DNA/RNA logic gates for in-vitro detection and in-vivo diagnosis and therapy.

Induction of autophagy by nanoparticles and their application in biomedicine

Autophagy, an important mechanism for maintaining cellular homeostasis, extensively participates in many physiological and pathological processes, and has become one of the hotspots in life sciences research. With more and more extensive application of nanoscience and nanotechnology to biomedicine, induction of autophagy by nanoparticles has attracted much attention by scientists and it becomes a new research direction in nanotoxicology and nanomedicine. This paper briefly introduces the basic situation of autophagy, including types of autophagy, internal/external stimuli, autophagy regulation and associated genes, as well as the great importance of autophagy in life sciences. According to the species of nanoparticles, it focuses on the induction of autophagy by nanoparticles and their application in biomedicine. It is pointed out that in further studies, autophagy induced by nanoparticles should be effectively regulated to prevent disease and promote health.

Nanoparticle-based regulation and imaging of cell autophagy

Autophagy is one of the essential metabolic processes in eukaryotic cells. It facilitates the clearance of redundant or damaged proteins and organelles. Autophagy contributes to cellular homeostasis via recycling of intracellular substances and providing energy. Overall, autophagy is a self-protective mechanism. Meanwhile, autophagy has complicated connection with apoptosis. Undesired up-regulation or inhibition of autophagy is closely related to the occurrence and development of various kinds of diseases, including neurodegenerative diseases, tumors, and microbial infections. Therefore, further understanding of the regulative mechanism of autophagy is likely to improve human health and has been actively explored in biomedical research. Especially, studies on cellular effects of nanomaterials under the context of autophagy have emerged as a novel area of interest. In this review, we summarize recent progress in the field of autophagy and focus on the applications of nanoparticles in autophagy regulation and imaging.

The application of silicon nanowire field-effecttransistor-based biosensors in molecular diagnosis

Cancer, one of the most life-threatening diseases, causes a heavy burden to both the society and family. Timely and efficient early diagnosis of cancer is critical to enable effective treatment and improving survival rate, which also is currently one of the most challenging problems in clinical medicine. Although modern medical imaging is an important tool for cancer diagnosis, detection of molecular biomarkers (such as DNA, RNA, proteins, and metabolites), released from the cancer cells or the organs, is the preferred approach for detecting and tracking cancer due to their unique association with genomic changes in cancer cells, especially for screening and early diagnosis of cancer. Molecular diagnosis can help doctors not only make a precise diagnosis in diseases’ early stage, but also make a judgment in disease staging, classification, curative effect monitoring and prognosis evaluation. A variety of conventional technologies are developed for biomarker detection, such as radio-immunoassay and enzyme-linked immunosorbent assay (ELISA), however, they are label-based, multi-step, time-consuming, and required experienced personnel to conduct the experiment. Silicon nanowire field-effect transistors (SiNW-FETs), as new one-dimensional semiconducting nanostructures, exhibit some unique properties, including high surface-to-volume ratios, fast electron transfer, and biocompatibility. SiNW-FET based biosensors have recently been attracted tremendous attention as a promising tool in biomedical and chemical detection because of their ultrasensitivity, specificity, label-free detection, and rapid and real-time response capabilities, which demonstrate a great potential in the application of medical diagnosis, chemical analysis, environmental monitoring, and food industry. Over the past decade, SiNW-FET biosensors are employed in the detections of DNA sequences, microRNAs, proteins, small molecules, cancer biomarkers, cells, and viruses. Here, we present a comprehensive review which introduces the working principle of SiNW-FETs, the fabrication of SiNWs, influence factors of the sensitivity, as well as the applications of SiNW-FET biosensors in cancers’ molecular diagnosis (including nucleic acid detection, biomarkers detection, and studies of molecule-molecule interactions). The future prospects in this area are also discussed, which can provide a guidance for the further applications in early diagnosis. SiNW-FET biosensors, as a promise tool in molecular diagnosis, held great potential applications in large-scale screening and point-of-care testing for early-stage cancer.