Dan Zhu

Bio: Dan Zhu is an academic researcher from Southeast University. The author has contributed to research in topics: Nanocarriers & Drug carrier. The author has an hindex of 15, co-authored 25 publications receiving 1109 citations.

SERS-Activated Platforms for Immunoassay: Probes, Encoding Methods, and Applications

Abstract: Owing to their excellent multiplexing ability, high sensitivity, and large dynamic range, immunoassays using surface-enhanced Raman scattering (SERS) as the readout signal have found prosperous applications in fields such as disease diagnosis, environmental surveillance, and food safety supervision. Various ever-increasing demands have promoted SERS-based immunoassays from the classical sandwich-type ones to those integrated with fascinating automatic platforms (e.g., test strips and microfluidic chips). As recent years have witnessed impressive progress in SERS immunoassays, we try to comprehensively cover SERS-based immunoassays from their basic working principles to specific applications. Focusing on several basic elements in SERS immunoassays, typical structures of SERS nanoprobes, productive optical spectral encoding strategies, and popular immunoassay platforms are highlighted, followed by their representative biological applications in the last 5 years. Moreover, despite the vast advances achieved ...

SERS detection and removal of mercury(II)/silver(I) using oligonucleotide-functionalized core/shell magnetic silica sphere@Au nanoparticles.

Abstract: Heavy metal ions, such as Hg2+ and Ag+, pose severe risks in human health and the environment. For sensitive detection and selective removal of Hg2+ and Ag+ ions, here, we demonstrate a surface-enhanced Raman scattering (SERS)-active platform by employing the oligonucleotide-functionalized magnetic silica sphere (MSS)@Au nanoparticles (NPs). This system exploits mismatched T–Hg–T and C–Ag–C bridges to capture Hg2+ and Ag+ ions, exhibiting excellent responses for Hg2+ ions in the range of 0.1–1000 nM and for Ag+ in the range of 10–1000 nM. The assay is highly selective for the target ions and does not respond to other metal ions. Additionally, the Hg2+ and Ag+ ions in this system can be effectively removed from surrounding solutions by an external magnetic field or through spontaneous precipitation. Moreover, more than 80% of the MSS@Au NPs can be easily recycled with the help of cysteine. We anticipate that the designed strategy could be extended to other analytes that can bind to DNA molecules with a hig...

pH and thermo dual-stimuli-responsive drug carrier based on mesoporous silica nanoparticles encapsulated in a copolymer-lipid bilayer.

Abstract: A pH and thermo dual-controllable composite structure was developed as a triggerable drug delivery carrier. In such a drug carrier, a mesoporous silica nanoparticle (MSN) acts as the drug loading core, while a layer of copolymer-lipid serves as the dual-responsive gating shell. Specifically, the copolymer-lipid bilayer consists of natural phospholipids (soy phosphatidylcholine, SPC) and the poly(N-isopropylacrylamide-methacrylic acid-octadecyl acrylate) (p(NIPAM-MAA-ODA)) copolymer. With this structure, a high drug loading capacity and a sustained release effect could be provided by the MSN core, while a pH and thermo dual-responsive releasing ability could be offered by the copolymer-lipid bilayer. In addition, the introduction of SPC instead of the traditionally used phospholipids (such as dioleoyl phosphatidylethanolamine (DOPE) or dipalmitoyl phosphatidylcholine (DPPC)) results in a much lower cost and a better serum stability. Using doxorubicin (DOX) as the drug model, our results confirmed that either pH or temperature can trigger the drug release. However, much more drugs could be released by simultaneously controlling the pH and temperature. Furthermore, after being cocultured with cancer cells (MCF-7), the drug carriers transported DOX into the cells and exhibited a pH-sensitive release behavior. Since most tumor sites usually exhibit a more acidic environment or a higher temperature, the pH- and thermo-responsive releasing ability of this drug carrier is particularly useful and important for the targeted release at the tumor region. Thus, due to the powerful controlled releasing ability, the straightforward preparation method, and low cost, the demonstrated nanocarrier will have potential applications in controllable drug delivery and cancer therapy.

Facile detection of tumor-derived exosomes using magnetic nanobeads and SERS nanoprobes

Abstract: Exosomes play an important role in intercellular communications. Here, we present a surface-enhanced Raman scattering (SERS) based detection method for tumor-derived exosomes using SERS nanoprobes and magnetic nanobeads. The SERS nanoprobe has a core–shell structure, with gold core–silver shell nanorods (Au@Ag NRs) as the SERS active core, Raman molecules as the SERS reporter and a silica layer as the protecting shell. The outmost surface of the SERS nanoprobe is decorated with exosome-specific antibodies. Each magnetic nanobead is fabricated by coating Fe3O4 nanoparticles (NPs) with a silica shell and attaching specific antibodies to the silica shell. With target exosomes present, the magnetic nanobeads and SERS nanoprobes can capture the exosomes by forming a sandwich-type immunocomplex. The immunocomplex (as well as the SERS nanoprobes) can be precipitated with a magnet, and thus SERS signals can be detected in the precipitates. With no target exosomes present, no immunocomplex can be formed, and thus quite weak SERS signals will be detected in the precipitates. Hence, the SERS signal of the final magnetic separation product can be used to detect exosomes. In the experiment, using one kind of tumor cells and one kind of normal cells, we proved that the presented method can be used for both qualitative and quantitative detection of tumor-derived exosomes.

Imaging and Intracellular Tracking of Cancer-Derived Exosomes Using Single-Molecule Localization-Based Super-Resolution Microscope.

Abstract: Exosomes are small membrane vesicles secreted by cells and enriched with plenty of proteins. Considering their significant roles in different physical activities and potential value for diagnostic drug delivery, researchers have put great efforts in in vitro tracking and content analysis of exosomes. Recently, the emergence of different kinds of super-resolution microscopy provides powerful tools for exosome study. Here, we demonstrate the application of single-molecule localization based super-resolution imaging technique in the imaging and tracking of cancer-derived exosomes. In the experiment, first, cancer-derived exosomes are extracted from the culture media of tumor cells. Then the exosome membrane receptors are labeled with photoswitchable probes, which allow super-resolution imaging of these membrane receptors via photoactivated localization microscopy (PALM) or stochastic optical reconstruction microscopy (STORM). By using human breast cancer cell-derived exosomes, we demonstrated simultaneous dual-color PALM/STORM imaging of two kinds of membrane receptors on the exosome membrane. Moreover, the successful labeling and imaging of exosomes make it possible to observe the interaction between cancer-derived exosomes and normal cells. Meanwhile, we realized the colocalization of cancer-derived exosomes and lysosomes in recipient cells with PALM/STORM imaging. Since exosomes play a vital role in intercellular communications, we anticipate that the presented PALM/STORM-based imaging and tracking of exosomes holds a great potential in the investigation of the mechanism of exosome-mediated cancer metastasis.

Minimal information for studies of extracellular vesicles 2018 (MISEV2018) : a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Present and Future of Surface-Enhanced Raman Scattering

Abstract: The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.

Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and Challenges

Abstract: Surface-enhanced Raman spectroscopy (SERS) inherits the rich chemical fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, most Raman peaks have a narrow width suitable for multiplex analysis, and the measurements can be conveniently made under ambient and aqueous conditions. These merits make SERS a very promising technique for studying complex biological systems, and SERS has attracted increasing interest in biorelated analysis. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biological questions, and solve fatal clinical problems. SERS applications in bioanalysis involve the complex interactions of plasmonic nanomaterials with biological systems and their environments. The reliability becomes the key issue of bioanalytical SERS in order to extract meaningful information from SERS data. This review provides a comprehensive over...

Fluorescence nanoscopy in cell biology

Abstract: Fluorescence nanoscopy uniquely combines minimally invasive optical access to the internal nanoscale structure and dynamics of cells and tissues with molecular detection specificity. While the basic physical principles of 'super-resolution' imaging were discovered in the 1990s, with initial experimental demonstrations following in 2000, the broad application of super-resolution imaging to address cell-biological questions has only more recently emerged. Nanoscopy approaches have begun to facilitate discoveries in cell biology and to add new knowledge. One current direction for method improvement is the ambition to quantitatively account for each molecule under investigation and assess true molecular colocalization patterns via multi-colour analyses. In pursuing this goal, the labelling of individual molecules to enable their visualization has emerged as a central challenge. Extending nanoscale imaging into (sliced) tissue and whole-animal contexts is a further goal. In this Review we describe the successes to date and discuss current obstacles and possibilities for further development.

Recent Advances on Graphene Quantum Dots: From Chemistry and Physics to Applications

Abstract: Graphene quantum dots (GQDs) that are flat 0D nanomaterials have attracted increasing interest because of their exceptional chemicophysical properties and novel applications in energy conversion and storage, electro/photo/chemical catalysis, flexible devices, sensing, display, imaging, and theranostics. The significant advances in the recent years are summarized with comparative and balanced discussion. The differences between GQDs and other nanomaterials, including their nanocarbon cousins, are emphasized, and the unique advantages of GQDs for specific applications are highlighted. The current challenges and outlook of this growing field are also discussed.