About
91
Publications
19,307
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,862
Citations
Introduction
The Nano-Thermal Bioengineering Laboratory (NT-BEL) focuses on fundamental understanding of biotansport issues for the brain and diagnostic systems, and develop nanotechnology-based approaches to better understand the brain and revolutionize point-of-care infectious disease diagnosis.
Skills and Expertise
Current institution
Publications
Publications (91)
Plasmonic nanomaterials are effective photoacoustic (PA) contrast agents with diverse biomedical applications. While silica coatings on gold nanoparticles (AuNPs) have been demonstrated to increase PA efficiency, the underlying mechanism remains elusive. Here, we systematically investigated the impact of silica coatings on PA generation under picos...
A phenol molecule is shown at its free energy minimum in a trans azo-PC lipid bilayer, where it interacts with the azobenzene groups that are incorporated into one of the two phosphatidylcholine lipid tails.
Neuromodulation aims to modulate the signaling activity of neurons or neural networks by the precise delivery of electrical stimuli or chemical agents and is crucial for understanding brain function and treating brain disorders. Conventional approaches, such as direct physical stimulation through electrical or acoustic methods, confront challenges...
Fluorescent gold nanoclusters (AuNCs) have shown promise as metal ion sensors. Further research into surface ligands is crucial for developing sensors that are both selective and sensitive. Here, we designed simple tripeptides to form fluorescent AuNCs, capitalizing on tyrosine’s reduction capability under alkaline conditions. We investigated tyros...
Janus nanoparticles (JNPs) with heterogeneous compositions or interfacial properties can exhibit directional heating upon external excitation with optical or magnetic energy. This directional heating may be harnessed for new nanotechnology...
Selective and remote manipulation of activity for biomolecules, including protein, DNA, and lipids, is crucial to elucidate the molecular function and to develop biomedical applications. While advances in tool development, such as optogenetics, have significantly impacted these directions, the requirement for genetic modification significantly limi...
The blood–brain barrier (BBB) is a major obstacle to the diagnostics and treatment of many central nervous system (CNS) diseases. A prime example of this challenge is seen in glioblastoma (GBM), the most aggressive and malignant primary brain tumor. The BBB in brain tumors, or the blood–brain–tumor barrier (BBTB), prevents the efficient delivery of...
The human brain represents one of the most complex biological systems, containing billions of neurons interconnected through trillions of synapses. Inherent to the brain is a biochemical complexity involving ions, signaling molecules, and peptides that regulate neuronal activity and allow for short- and long-term adaptations. Large-scale and noninv...
Live imaging of the brain extracellular matrix (ECM) provides vital insights into changes that occur in neurological disorders. Current techniques such as second or third‐harmonic generation offer limited contrast for live imaging of the brain ECM. Here, a new method, pan‐ECM via chemical labeling of extracellular proteins, is introduced for live b...
Glioblastoma (GBM) is the most complex and lethal adult primary brain cancer. Adequate drug diffusion and penetration are essential for treating GBM, but how the spatial heterogeneity in GBM impacts drug diffusion and transport is poorly understood. Herein, we report a new method, photoactivation of plasmonic nanovesicles (PANO), to measure molecul...
Optical tweezers have profound importance across fields ranging from manufacturing to biotechnology. However, the requirement of refractive index contrast and high laser power results in potential photon and thermal damage to the trapped objects, such as nanoparticles and biological cells. Optothermal tweezers have been developed to trap particles...
The treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human g...
The blood–brain barrier (BBB) is a dynamic regulatory barrier at the interface of blood circulation and the brain parenchyma, which plays a critical role in protecting homeostasis in the central nervous system. However, it also significantly impedes drug delivery to the brain. Understanding the transport across BBB and brain distribution will facil...
Janus nanoparticles (JNPs) with heterogeneous compositions or interfacial properties can exhibit directional heating upon external excitation, such as laser radiation and magnetic field. This directional heating may be harnessed for new nanotechnology and biomedical applications. Understanding thermal transport and temperature control with JNP heat...
Many diseases affecting the central nervous system (CNS) are deadly but less understood, leading to impaired mental and motor capabilities and poor patient prospects. Gene therapy is a promising therapeutic modality for correcting many genetic disorders, expanding in breadth and scope with further advances. This review summarizes the candidate CNS...
The brain extracellular matrix (ECM), consisting of proteins and glycosaminoglycans, is a critical scaffold in the development, homeostasis, and disorders of the central nervous system (CNS) and undergoes remodeling in response to environmental cues. Live imaging of brain ECM structure represents a native view of the brain ECM but, until now, remai...
Plasmonic gold nanostructures are a prevalent tool in modern hypersensitive analytical techniques such as photoablation, bioimaging, and biosensing. Recent studies have shown that gold nanostructures generate transient nanobubbles through localized heating and have been found in various biomedical applications. However, the current method of plasmo...
Neuropeptides are abundant and essential signaling molecules in the nervous system involved in modulating neural circuits and behavior. Neuropeptides are generally released extrasynaptically and signal via volume transmission through G-protein-coupled receptors (GPCR). Although substantive functional roles of neuropeptides have been discovered, man...
The blood-brain barrier (BBB) maintains an optimal environment for brain homeostasis but excludes most therapeutics from entering the brain. Strategies that reversibly increase BBB permeability are essential for treating brain diseases and are the focus of significant preclinical and translational interest. Picosecond laser excitation of tight junc...
Optical tweezers have profound importance across fields ranging from manufacturing to biotechnology. However, the requirement of refractive index contrast and high laser power results in potential photon and thermal damage to the trapped objects, such as nanoparticles and biological cells. Optothermal tweezers have been developed to trap particles...
Point-of-care detection of pathogens is critical to monitor and combat viral infections. The plasmonic coupling assay (PCA) is a homogeneous assay and allows rapid, one-step, and colorimetric detection of intact viruses. However, PCA lacks sufficient sensitivity, necessitating further mechanistic studies to improve the detection performance of PCA....
Point-of-care (POC) tests for the diagnosis of diseases are critical to the improvement of the standard of living, especially for resource-limited areas or countries. In recent years, nanobiosensors based on noble metal nanoparticles (NM NPs) have emerged as a class of effective and versatile POC testing technology. The unique features of NM NPs en...
Plasmonic gold nanoparticles (AuNPs) are effective photoacoustic (PA) signal agents and have found important biomedical applications. The silica coating on the surface of AuNPs showed enhanced PA efficiency, however, the PA amplification mechanism remains unclear. Here, we systematically studied the silica coating effect on PA generation of AuNPs u...
Precise modulation of neuronal activity by neuroactive molecules is essential for understanding brain circuits and behavior. However, tools for highly controllable molecular release are lacking. Here, we developed a photoswitchable nanovesicle with azobenzene-containing phosphatidylcholine (azo-PC), coined ‘azosome’, for neuromodulation. Irradiatio...
Point-of-care detection of pathogens is critical to monitor and combat viral infections. Here, we demonstrate a plasmonic coupling assay (PCA) using gold nanourchins (AuNUs) as labels for the colorimetric quantification of viruses. The antibody functionalized AuNUs allow for rapid and highly specific identification of viruses and provide strong col...
Neuropeptides are abundant signaling molecules in the central nervous system. Yet remarkably little is known about their spatiotemporal spread and biological activity. Here, we developed an integrated optical approach using Plasmonic nAnovesicles and cell‐based neurotransmitter fluorescent engineered reporter (CNiFER), or PACE, to probe neuropeptid...
p>Plasmonic gold nanoparticles (AuNPs) can convert laser irradiation into thermal energy for a variety of applications. Although heat transfer through the AuNP-water interface is considered an essential part of the plasmonic heating process, there is a lack of mechanistic understanding of how interface curvature and the heating itself impact interf...
Precise modulation of neuronal activity by neuroactive molecules is essential for understanding brain circuits and behavior. However, tools for highly controllable molecular release are lacking. Here, we developed a photoswitchable nanovesicle with azobenzene-containing phosphatidylcholine (azo-PC), coined ‘azosome’, for neuromodulation. Irradiatio...
Glioblastoma multiforme (GBM) is the most prevalent malignant tumor in the central nervous system. It has diverse phenotypes, including diffuse single-cell infiltration in which the tumor cells co-opt the normal microvasculature, and the neovascularization of an expanding tumor mass. The blood-brain-tumor barrier (BBTB) is a significant obstacle to...
The blood-brain barrier (BBB) maintains an optimal environment for brain homeostasis but excludes most therapeutics from entering the brain. Strategies that can reversibly increase BBB permeability will be essential for treating brain diseases and is the focus of significant preclinical and translational interest. Recently, we reported that picosec...
Neuropeptides are abundant signaling molecules in the central nervous system. Yet remarkably little is known about their spatiotemporal spread and biological activity. Here, we developed an integrated optical approach using P lasmonic n A novesicles and cell‐based neurotransmitter fluorescent engineered reporter ( C NiF E R), or PACE, to probe neur...
The blood-spinal cord barrier (BSCB) tightly regulates molecular transport from the blood to the spinal cord. Herein, we present a novel approach for transient modulation of BSCB permeability and localized delivery of peptides into the spinal cord for behavior modulation with high spatial resolution. This approach utilizes optical stimulation of va...
Diffusion of substances in the brain extracellular space (ECS) is important for extrasynaptic communication, extracellular ionic homeostasis, drug delivery, and metabolic waste clearance. However, substance diffusion is largely constrained by the geometry of brain ECS and the extracellular matrix. Investigating the diffusion properties of substance...
With the ability to convert external excitation into heat, nanomaterials play an essential role in many biomedical applications. Two modes of nanoparticle (NP) array heating, nanoscale-confined heating (NCH) and macroscale-collective heating (MCH), have been found and extensively studied. Despite this, the resulting biological response at the prote...
Over the past decade, various fluorescent gold nanoclusters (AuNCs) have been studied for their potential as metal ion sensors. Due to the importance of the surface ligand in stabilizing nanocluster and sensing target metal ions, there is a great need of further investigations into possible surface ligands to develop selective and sensitive sensors...
Rapid and sensitive diagnostics of infectious diseases is an urgent and unmet need as evidenced by the COVID-19 pandemic. Here, we report a strategy, based on DIgitAl plasMONic nanobubble Detection (DIAMOND), to address this need. Plasmonic nanobubbles are transient vapor bubbles generated by laser heating of plasmonic nanoparticles (NPs) and allow...
Ischemic stroke is a leading cause of death and disability and remains without effective treatment options. Improved treatment of stroke requires efficient delivery of multimodal therapy to ischemic brain tissue with high specificity. Here, this article reports the development of multifunctional polymeric nanoparticles (NPs) for both stroke treatme...
SARS‐CoV‐2 Testing In article number 2107832, Leonidas Bleris, Zhenpeng Qin, and co‐workers develop a plasmonic sensing method for loop‐mediated isothermal amplification (plasmonic LAMP). It turns complex amplicons into short single‐strand DNA for sequence‐specific detection with plasmonic nanoprobes, achieving improved detection sensitivity and sp...
The ability to detect pathogens specifically and sensitively is critical to combat infectious diseases outbreaks and pandemics. Colorimetric assays involving loop‐mediated isothermal amplification (LAMP) provide simple readouts yet suffer from the intrinsic non‐template amplification. Herein, a highly specific and sensitive assay relying on plasmon...
To precisely control protein activity in a living system is a challenging yet long-pursued objective in biomedical sciences. Recently, we have developed a new approach named molecular hyperthermia (MH) to photoinactivate protein activity of interest without genetic modification. MH utilizes nanosecond laser pulse to create nanoscale heating around...
Plasmonic gold nanoparticles (AuNPs) can convert laser irradiation into thermal energy and act as nano heaters in avariety of applications. Although the AuNP-water interface is an essential part of the plasmonic heating process,there is a lack of mechanistic understanding of how interface curvature and the heating itself impact interfacial heattran...
Nanoparticle (NP) are promising agents to absorb external energy excitation and generate heat. Cluster of NPs or NP array heating have found essential roles for biomedical applications, diagnostic techniques and chemical catalysis. Various studies have shed light on the heat transfer of nanostructures and greatly advanced our understanding of NP ar...
With the ability to convert external excitation into heat, nanomaterials play an essential role in many biomedical applications. Two modes of nanoparticle (NP) array heating, nanoscale-confined heating (NCH) and macroscale-collective heating (MCH), have been found and extensively studied. Despite this, the resulting biological response at protein l...
Single-molecule detection of pathogens such as SARS-CoV-2 is key to combat infectious diseases outbreak and pandemic. Currently colorimetric sensing with loop-mediated isothermal amplification (LAMP) provides simple readouts but suffers from intrinsic non-template amplification. Herein, we report that plasmonic sensing of LAMP amplicons via DNA hyb...
Neuropeptides are essential signaling molecules in the nervous system involved in modulating neural circuits and behavior. Although hypothesized to signal via volume transmission through G-protein coupled receptors (GPCR), remarkably little is known about their extrasynaptic diffusion. Here, we developed an all-optical approach to probe neuropeptid...
Nanoparticle (NP) are promising agents to absorb external energy excitation and generate heat. Cluster of NPs or NP array heating have found essential roles for biomedical applications, diagnostic techniques and chemical catalysis. Various studies have shed light on the heat transfer of nanostructures and greatly advanced our understanding of NP ar...
Understanding the laser-nanomaterials interaction including nanomaterial fragmentation has important implications in nanoparticle manufacturing, energy, and biomedical sciences. So far, three mechanisms of laser-induced fragmentation have been recognized including non-thermal processes and thermomechanical force under femtosecond pulses, and the ph...
Understanding the signal transmission and processing within the central nervous system is a grand challenge in neuroscience. The past decade has witnessed significant advances in the development of new tools to address this challenge. Development of these new tools draws diverse expertise from genetics, materials science, electrical engineering, ph...
Rapid and sensitive diagnostics of infectious diseases is an urgent and unmet need as evidenced by the COVID-19 pandemic. Here we report a novel strategy, based on DIgitAl plasMONic nanobubble Detection (DIAMOND), to address these gaps. Plasmonic nanobubbles are transient vapor bubbles generated by laser heating of plasmonic nanoparticles and allow...
Lateral flow assays (LFAs) are paper-based point-of-care (POC) diagnostic tools that are widely used because of their low cost, ease of use, and rapid format. Unfortunately, traditional commercial LFAs have significantly poorer sensitivities (μM) and specificities than standard laboratory tests (enzyme-linked immunosorbent assay, ELISA: pM–fM; poly...
To precisely control protein activity in a living system is a challenging yet long-pursued objective in biomedical sciences. Recently we have developed a new approach named molecular hyperthermia (MH) to photoinactivate protein activity of interest without genetic modification. MH utilizes nanosecond laser pulse to create nanoscale heating around p...
The blood-brain barrier (BBB) tightly regulates the entry of molecules into the brain by tight junctions that seals the paracellular space and receptor-mediated transcytosis. It remains elusive to selectively modulate these mechanisms and to overcome BBB without significant neurotoxicity. Here we report that light stimulation of tight junction-targ...
To precisely control protein activity in a living system is a challenging yet long-pursued objective in biomedical sciences. Recently we have developed a new approach named molecular hyperthermia (MH) to photoinactivate protein activity of interest without genetic modification. MH utilizes nanosecond laser pulse to create nanoscale heating around p...
Remote and minimally‐invasive modulation of biological systems with light has transformed modern biology and neuroscience. However, light absorption and scattering significantly prevents penetration to deep brain regions. Herein, we describe the use of gold‐coated mechanoresponsive nanovesicles, which consist of liposomes made from the artificial p...
Lateral flow assay (LFA) has become one of the most widely used point-of-care diagnostic methods due to its simplicity and low cost. While easy to use, LFA suffers from its low sensitivity and poor quantification, which largely limits its applications for early disease diagnosis and requires further testing to eliminate false-negative results. Over...
Remote and minimally‐invasive modulation of biological systems with light has transformed modern biology and neuroscience. However, light absorption and scattering significantly prevents penetration to deep brain regions. Here we describe the use of gold‐coated mechanoresponsive nanovesicles, which consist of liposomes made from the artificial phos...
Understanding protein folding and unfolding has been a long-standing fundamental question and have important applications in manipulating protein activity in biological systems. Experimental investigations of protein unfolding have been predominately conducted by small temperature perturbations (e.g. temperature jump), while molecular simulations a...
p>
In this article, we show that the surface of the bacteriophage Qβ is equipped with natural ligands for the synthesis of small gold nanoparticles. By exploiting disulfides in the protein secondary structure and the geometry formed from the capsid quaternary structure, we find we can produce regularly arrayed patterns of ~6 nm gold nanoparticles...
Plasmonic vesicle consists of multiple gold nanocrystals within a polymer coating or around a phospholipid core. As a multifunctional nanostructure, it has unique advantages of assembling small nanoparticles (<5 nm) for rapid renal clearance, strong plasmonic coupling for ultrasensitive biosensing and imaging, and near‐infrared light absorption for...
Efficient delivery to the cell nucleus remains a significant challenge for many biomolecules, including anticancer drugs, proteins and DNAs. Despite numerous attempts to improve nuclear import including using nucleus localization signal (NLS) peptides and nanoparticle carriers, they are limited by the nanoparticle size, conjugation method, dependen...
Gold nanoparticle (GNP)-based aggregation assay is simple, fast, and employs a colorimetric detection method. Although previous studies have reported using GNP-based colorimetric assay to detect biological and chemical targets, a mechanistic and quantitative understanding of the assay and effects of GNP parameters on the assay performance is lackin...
Vesicular assembly of small plasmonic nanoparticles, or plasmonic vesicle, is a promising multifunctional theranostic platform for photothermal therapy, near infrared (NIR) light-responsive drug release, and rapid clearance of small inorganic particles from the body. Wide ranges of optical properties are reported including characteristic absorption...
Zebrafish embryos can attain a stable cryogenic state by microinjection of cryoprotectants followed by rapid cooling, but the massive size of the embryo has consistently led to failure during the convective warming process. Here we address this zebrafish cryopreservation problem by using gold nanorods (GNRs) to assist in the warming process. Specif...
The possibility of regulating cell signaling with high spatial and temporal resolution within individual cells and complex cellular networks has important implications in biomedicine. This article demonstrates a general strategy that uses near-infrared tissue-penetrating laser pulses to uncage biomolecules from plasmonic gold-coated liposomes, i.e....
There is an increasing need for highly sensitive and quantitative diagnostics at the point-of-care. The lateral flow immunoassay (LFA) is one of the most widely used point-of-care diagnostic tests; however, LFAs generally suffers from low sensitivity and lack of quantification. To overcome these limitations, thermal contrast amplification (TCA) is...
Gold nanoparticles (GNPs) are widely used for biomedical applications due to unique optical properties, established synthesis methods, and biological compatibility. Despite important applications of plasmonic heating in thermal therapy, imaging, and diagnostics, the lack of quantification in heat generation leads to difficulties in comparing the he...
Thermal denaturation of proteins is critical to cell injury, food science and other biomaterial processing. For example protein denaturation correlates strongly with cell death by heating, and is increasingly of interest in focal thermal therapies of cancer and other diseases at temperatures which often exceed 50 °C. The Arrhenius model is a simple...
Cryptococcal meningitis is common in sub-Saharan Africa. Given the need for data for a rapid, point-of-care cryptococcal antigen (CRAG) lateral flow immunochromatographic assay (LFA), we assessed diagnostic performance of cerebrospinal fluid (CSF) culture, CRAG latex agglutination, India ink microscopy, and CRAG LFA for 832 HIV-infected persons wit...
Irreversible electroporation (IRE) is a promising technology to treat local malignant cancer using short, high-voltage electric pulses. Unfortunately, in vivo studies show that IRE suffers from an inability to destroy large volumes of cancer tissue without introduction of cytotoxic agents and/or increasing the applied electrical dose to dangerous l...
Irreversible electroporation (IRE) has been proposed to destroy large amounts of tumorous tissue and shows advantages over thermal therapies. Unfortunately, carefully constructed studies assessing impact in in vivo tumor systems and a direct comparison of IRE with thermal therapy are lacking. In this study, we investigate the effect of IRE in a hum...
Recently, irreversible electroporation (IRE) has emerged as a promising tumor ablation technique. IRE induces cell death by irreversibly compromising membrane integrity with a series of short, high voltage electrical pulses [1]. IRE offers many advantages over surgery and thermal ablations including that it 1) is fast and minimally invasive, 2) des...
The rapidly evolving field of nanomedicine focuses on the design and application of multi-functional nanoparticles for diagnosis and treatment of diseases especially cancer1. Many of these nanomaterials are designed to serve as drug delivery or image contrast agents, or even to generate heat for hyperthermia (i.e. treatment), of cancer. Heating exa...
Heat beyond visual: The thermal contrast from the heating of gold nanoparticles upon laser stimulation can improve the analytical sensitivity of lateral flow assays (LFAs; see picture). A 32-fold improvement in sensitivity of an approved LFA for cryptococcal antigen (purple diamond) was shown, with the potential for further improvement by optimizin...
A compelling vision in nanomedicine is the use of self directed nanoparticles that can accumulate in areas of disease to perform designed functions, such as molecular delivery or destruction, endosomal release of genes or siRNA, and selective cell or tumor destruction with nano to macroscale spatiotemporal control and precision. These functions are...
With the recent advance in micro/nano-fabrication technology, micro Coulter counters have been widely used in detecting and characterizing micro- and nanoscale objects. In this paper, the electrical resistance change during translocation of a non-conducting particle through a channel is studied numerically. The numerical results are validated by pr...
Biomedical applications of nanoparticle heating range in scale from molecular activation (i.e. molecular beacons, protein denaturation, lipid melting and drug release), cellular heating (i.e. nanophotolysis and membrane permeability control and rupture) to whole tumor heating (deep and superficial). This work will present a review on the heating of...
Intensive efforts have been put into the use of gold nanoparticles (GNPs) for the enhancement of hyperthermia using laser in recent years since the groundbreaking work of Hirsh et al.(1) using gold nanoshells (GNS). Both in vitro (2), and in vivo (3) studies show promising results. For example, GNS, a special kind of GNP, are being manufactured and...