Research Highlights
The Future of Neurology- Beyond Animal Models: Neurovascular Modeling for Personalized Medicine
The human neurovascular system is a complex network of blood vessels and brain cells essential to the proper functioning of the brain. In recent years, researchers have become increasingly interested in the role of this system in developing drugs to treat neuroinflammation. This process is believed to contribute to the development of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. While much remains to be learned about the precise mechanisms by which the neurovascular system interacts with the brain and how it can be targeted for therapeutic purposes, this area of research holds great promise for the future of neurology and medicine. Currently, creating neurovascular models begins with animal models, followed by testing on humans in clinical trials. However, the high number of medication failures that pass through animal testing indicates that animal models do not always reflect the outcome of human clinical trials. To overcome the challenges of neurovascular systems and the issues with animal models, Prof. Ki-Bum Lee and his team (https://kblee.rutgers.edu/) in the Department of Chemistry and Chemical Biology at Rutgers University reported the development of an innovative 'neuroinflammation-on-a-chip' combined with a nanobiosensing system to i) overcome the limitations of existing 3D neural cell culture systems, ii) detect neuroinflammation signals in a sensitive and real-time manner, and iii) facilitate the progress of human organ-on-a-chip technology.
A New Road for Treating Severe Intervertebral Disc Injuries and Diseases Using Novel Protein Nanoscaffold
Degeneration of fibrocartilaginous tissue is often associated with dysregulated inflammatory signaling. Such dysregulation is typically mediated by various factors, including reactive oxygen species (ROS), cell-free nucleic acids (cf-NAs), and changes in immune cell epigenetics. To effectively modulate complicated, inflammatory signaling, Dr. KiBum Lee’s team (https://kblee.rutgers.edu/) at Rutgers CCB developed a nanoscaffold-based approach of self-therapeutic 3D porous hybrid protein (3D-PHP) and then collaborated with Dr. Inbo Han from CHA University to demonstrate its therapeutic effects in the treatment of intervertebral disc (IVD) degeneration. This work has three significant points related to the fields of chemistry, biomaterials, and tissue engineering.
How Nanotechnology Can Help Prevent and Treat Chemotherapy Side Effects in Breast and Ovarian Cancer Survivors
Nanotechnology approaches have emerged as a promising strategy for the targeted and selective delivery of therapeutic agents. Hence, it is critical to investigate the development of nanomaterials that can be used to selectively deliver chemotherapeutics and help mitigate the unwanted effects of chemotherapy. Specifically, breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases. However, chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy are common side effects affecting breast and ovarian cancer survivors' quality of life. Therefore, there is an urgent need to develop effective prevention and treatment strategies for these adverse effects.
Nanoparticle-Based Artificial Mitochondrial DNA Transcription Factor: MitoScript
Aberrant transcription of mitochondrial DNA (mtDNA) has been linked to many diseases and neurological disorders in the human body. Consequently, novel and effective means of site-specific mtDNA transcriptional regulation have become indispensable in the quest to study and treat such disorders. However, current approaches to modulating mtDNA transcription are confronted with significant hurdles in intracellular transport and blood circulation, thereby presenting a formidable challenge to attaining maximum efficiency. To this end, nanoparticles can be designed to be specifically targeted to the affected area, ensuring the drug reaches the exact location it needs to in order to be effective. This allows for more accurate and efficient delivery of the drug or genetic materials, causing no unnecessary harm to the patient. Furthermore, nanoparticles can improve the solubility of the drug, allowing it to be more easily absorbed into the body. This, in turn, leads to improved efficacy of the therapeutics. Nonetheless, the demand for direct, efficacious, and target-specific modulation of mitochondrial gene expression remains unfulfilled.
Nanohybrid Peptide Hydrogel for Enhanced Intervertebral Disc Repair and Regeneration
Injuries to fibrocartilaginous tissues can cause significant pain and loss of mobility. Regenerating these tissues, such as the intervertebral disc (IVD), is difficult for a variety of reasons, including limited innate regenerative capacity, pro-inflammatory signals, toxic reactive oxygen species (ROS), and multiscale tissue architectures (macro- and microscopic features). Because of these obstacles, the regeneration of damaged IVD necessitates the utilization of biomaterials that are both multiscale and multifunctional.
In a recent publication, Prof. Ki-Bum Lee and his research team (https://kblee.rutgers.edu/) collaborated with Prof. Inbo Han (CHA University, https://sites.google.com/view/inbolab/home) to develop a nanomaterial-augmented hydrogel for IVD treatment [Figure 1].
Incorporation of an Isohexide Subunit Improves the Drug-like Properties of Bioactive Compounds
ABOUT THE COVER: An isohexide substructure bridges the conceptual gap between potent bioactive compounds and those that also exhibit suitable drug-likeness properties.
A recent paper by Spencer Knapp and his group has recently been published in ACS Medicinal Chemistry Letters along with the journal cover featuring this work.
Effective new methods to streamline drug development and address issues of drug-likeness earlier in the process would lead to savings in time and expense. We have found that incorporation of an isohexide substructure into bioactive molecules can dramatically improve their solubility, permeability, bioavailability, and other attributes.
Theragnostic Functional Nanoparticles for the Central Nervous System
In recent years, there has been a surge of interest in using functional inorganic nanomaterials as theragnostic agents to diagnose and treat diseases of the central nervous system (CNS). Functional nanomaterials provide a plethora of physical and chemical stimuli capable of facilitating targeted delivery, promoting cellular proliferation and differentiation, and delivering quantifiable signals that can be leveraged to efficiently and accurately diagnose patients. Compared to their organic counterparts, inorganic nanomaterials possess intrinsic properties that arise from their chemical composition and crystalline structure, which can be easily tuned to impart magnetic, optical, and various other modalities to a material platform. Although there is increasing amount of research effort in this area, there is not yet a thorough study covering the application of theragnostic inorganic nanoparticles in the CNS.
High-Content Screening and Analysis of Stem Cell-Derived Neural Interfaces Using a Combinatorial Nanotechnology and Machine Learning Approach
Systematically understanding the interactions between stem cell fate control and nanotopographies can significantly facilitate the discovery of the molecular mechanisms behind cell behavior in neurological disorders and accelerate the development of stem cell-based therapies. However, high-throughput investigation of the cell-type-specific biophysical cues associated with stem cell-derived neural interfaces continues to be a significant obstacle to overcome. To accomplish this goal, Prof. Ki-Bum Lee and his research team (https://kblee.rutgers.edu/) developed a combinatorial nanoarray-based method for high-throughput investigation of neural interface micro-/nanostructures (physical cues comprising geometrical, topographical, and mechanical aspects) and the effects of these complex physical cues on stem cell fate decisions.
Injectable bioorthogonal hydrogel (BIOGEL) accelerates tissue regeneration in degenerated intervertebral discs
Intervertebral disc (IVD) degeneration is a leading cause of back pain and precursor to more severe conditions, including disc herniation and spinal stenosis. Traditional growth factor therapies (e.g., TGFβ) are insufficient to regenerate damaged tissue, while most IVD replacements involve synthetic or non-mammalian polymers with limited biological function. Moreover, the process of implanting treatments can cause further damage to the IVD. Therefore, a new generation of injectable treatments using bioactive materials is needed to treat IVD degeneration.
To address these challenges, Prof. Ki-Bum Lee and his research team (https://kblee.rutgers.edu/) partnered with Prof. Inbo Han (CHA University, https://sites.google.com/view/inbolab/home) to develop an injectable hydrogel to treat IVD degeneration [Figure 1].
Figure 1
Effective Separation of Xylene Isomers by a Chain-like Coordination Polymer
Xylene isomers are important raw chemicals used for manufacturing a variety of industrial commodities. However, separation of these isomers by either distillation or adsorption remains a challenging process because they have very
similar molecular size, shape and physical properties (e.g., nearly the same boiling points). The distillation method is extremely energy intensive, while the adsorption method using conventional adsorbent (e.g. zeolites) suffers from low selectivity and often requires high temperature. Developing highly efficient adsorbents with excellent adsorption capacity and selectivity is crucial for the implementation of simulated moving bed (SMB) technology for the industrial separation and purification of the xylene isomers. In a very recent work published in Science, the research teams of Prof. Jing Li (Rutgers University, https://chem.rutgers.edu/jinglilab) and Prof. Zongbi Bao (Zhejiang University) reported the use of a stacked one-dimensional (1D) coordination polymer, [Mn(dhbq)(H2O)2] (H2dhbq = 2,5-dihydroxy-1,4-benzoquinone) to effectively separate the three xylene isomers. The unique temperature-adsorbate dependent adsorption behavior of the polymer enables full separation of p-, m- and o-xylene isomers in both vapor and liquid phase. The delicate stimuli-responsive swelling of the structure endows this porous material with exceptionally high flexibility, stability, and well-balanced adsorption capacity, high selectivity and fast kinetics at conditions mimicking industrial settings. This study may offer an alternative approach for energy-efficient, adsorption-based industrial separation and purification of xylene isomers
PUBLICATION: Li, L.Y.; Guo, L.D.; Olson, D.H.; Xian, S.K.; Zhang, Z.G.; Yang, Q.W.; Wu, K.Y.; Yang, Y.W.; Bao, Z.B; Ren, Q.L.; Li, J. “Discrimination of Xylene Isomers in A Stacked Coordination Polymer”, Science, 2022, 377, 335-339, DOI: 10.1126/science.abj7659.
Magnetic Nanomaterials for Extracellular Vesicles
In the past decade, scientists in fields of biology, material science, and bioengineering have witnessed a surge of interest in extracellular vesicle-based diagnostic and therapeutic applications. There has also been a strong push for translating extracellular vesicles into clinical treatment of diseases recently, as evidenced by many clinical trials. To facilitate the isolation, capturing, analysis, delivery, monitoring, and imaging of extracellular vesicles for biomedical applications, magnetic nanomaterials have already played significant roles, with over 300 published articles on this topic. Despite a continuous surge of research activity in this field, a comprehensive review covering magnetic nanomaterial-based detection, delivery, and engineering of extracellular vesicles for biomedical applications is lacking.
Detecting Mutated SARS-CoV-2 Viral RNAs Using an Advanced Nanodevices
In biomedical applications, sensitive and selective detection of nucleic acids and their mutation variants is critical. Although various nucleic acid biosensors have been developed, they frequently require pre-treatment activities such as target amplification and nucleic acid tagging. Furthermore, present biosensors are often incapable of detecting sequence-specific alterations in the nucleic acids under study. As a result, there is an urgent need to develop a nucleic acid detection approach that does not rely on typical target amplification and tagging processes, all of which can allow us to identify virus alterations quickly and easily.
Direct Cell Reprogramming and Cooperative Epigenetic Modulation via Hierarchical Nanostructures Screened from Comprehensive Biophysical Cue Mapping
Although direct cell reprogramming has great promise for cell-based tissue engineering and regenerative medicine, realizing its full therapeutic potential necessitates more precise control of cell fate and a systematic understanding of the corresponding cellular responses to the surrounding microenvironment. Biophysical cues, such as extracellular matrix (ECM) nanotopographies, are important cell regulators for direct cell reprogramming. As a result, high throughput approaches for screening a wide range of biophysical cue-regulated cell reprogramming are becoming increasingly important for tissue engineering and regenerative medicine.
Advancing Organoid Research Using Bionanotechnology Approaches
Stem cells are characterized by a unique ability to self-renew and differentiate and have revolutionized modern biological sciences and medical researches with unique approaches for understanding developmental processes and disease modeling. With recent advances in 3D cell culture technology, stem cells are allowed to reside in culture environments emancipating their intrinsic self-organizing properties and form into “organoids” resembling structural as well as functional characteristics of organs [Figure 1]. To advance organoid development, diverse advanced material and engineering techniques have been incorporated into conventional organoid culture methods [Figure 1]. Despite the wide use of organoids and the recent surge of research activity in this field, a comprehensive review covering engineering extracellular matrices to support organoid culture for developmental studies, 3D organ-level biology, and bioengineering-based disease modeling is lacking.
SMART SPHEROID-BASED STEM CELL THERAPY FOR EFFECTIVE SCI TREATMENTS
Cell therapy holds great potential for treating various incurable diseases and disorders, including spinal cord injury (SCI). However, cell death and a lack of control of cell fate limit the clinical application of cell therapies, especially stem cell therapies. Therefore, there is a critical need to develop novel methods to promote cell survival and control of cell fate after transplantation of cells.
Addressing these challenges, Prof. Ki-Bum Lee and his team (https://kblee.rutgers.edu/) in the Department of Chemistry and Chemical Biology at Rutgers developed hybrid nanomaterial-enhanced stem-cell spheroids to tackle some of the major challenges associated with cell therapies [Figure 1].
CRISPR/Cas-based Nanobiosesning for advanced virus detection
Viral diseases have received immense attention in the medical and healthcare fields because of the high transmission rates and difficulty in curing, including the recent COVID-19 issue. Nucleic acids are one of the attractive biomarkers to diagnose various viral-associated diseases precisely. Recently, the target nucleic acid-dependent trans-activating phenomenon of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas has shown huge potential for developing sensitive and selective biosensors to detect targeted nucleic acids. However, the nucleic acid amplification steps are conventionally required for sensitive and selective monitoring of the target nucleic acid, requiring multistep reactions, expensive reagents, well-trained personnel, and sophisticated instrumentation.
Hybrid Graphene‐Gold Nanoparticle‐Based Nucleic Acid Conjugates for Cancer‐Specific Multimodal Imaging and Combined Therapeutics
Intelligent Drug Delivery Platform Developed for Personalized Cancer Treatment
Scheme: An intelligent drug delivery platform composed of thin carbon (graphene)-coated gold nanoparticles is developed for target-specific multimodal cancer therapies and imaging. Image credit: Letao Yang and Ki-Bum Lee.
A team from the Department of Chemistry and Chemical Biology at Rutgers has created an intelligent drug delivery platform that effectively induces apoptotic signaling and may help the personalized treatment of cancer patients.
Effective Modulation of CNS Inhibitory Microenvironment using Bioinspired Hybrid‐Nanoscaffold‐Based Therapeutic Interventions
Prof. Ki-Bum Lee’s group at the Chemistry and Chemical Biology Department in Rutgers has led the development of an advanced spatiotemporally controlled in vivo drug delivery system for effective modulation of neuroinflammation that may help the treatment of spinal cord injury and other neurological disorders.
FIGURE DESCRIPTION: Current biomaterials‐based treatment of central nervous system (CNS) injuries has been hampered by the resulting neuroinhibitory microenvironment. By targeting two critical neuroinhibitory factors in a single platform, a biomimetic 3D porous hybrid nanoscaffold is created by developing viscous interfacial self‐assembly. The nanoscaffold‐based therapeutic interventions achieve functional recovery through reducing neuroinflammation and fibrotic scarring, thereby paving a new road for the biomaterials‐based treatment of CNS injuries.
In Situ Detection of Neurotransmitters from Stem Cell-Derived Neural Interface at the Single-Cell Level via Graphene-Hybrid SERS Nanobiosensing
A graphene oxide (GO)-hybrid nanosurface-enhanced Raman scattering (SERS) array was developed by a Rutgers team to detect dopamine (DA) selectively and sensitively. Using the GO-hybrid nano-SERS array, a wide range of DA concentrations was detected rapidly and reliably, thereby enabling the measurement of DA from differentiating neural stem cells and the characterization of neuronal differentiation. Given the challenges of in situ detection of neurotransmitters at the single-cell level, our developed SERS-based detection method can represent a unique tool for investigating single-cell signaling pathways associated with DA, various other neurotransmitters, and their roles in neurological signalling.
4D Printing Technology Meets High Throughput Stem Cell Research
3D stem cell assembles such as spheroids and organoids are becoming increasingly popular to mimic complex interactions that are typically absent in traditional 2D cell culture. Unfortunately, 3D cell culture characterization techniques such as histology can be technically challenging, time-consuming, and labor-intensive when processing numerous samples. To make 3D cell culture more accessible and encourage further research using these technologies, high-throughput devices must be developed to facilitate characterization and downstream applications.
Remote Control of Stem Cell Differentiation Using NIR Light
Stem cell functions and fates are dynamically orchestrated by various biomolecular as well as physical signals in a spatially and temporally controlled manner. Achieving precise control of stem cell fates and functions is of great significance for studying physiological mechanisms, identifying pathogenic pathways, and developing enhanced treatments of devastating diseases. To better investigate and further regulate these complex biological processes, photo-responsive nanomaterials have gained increasing research interests for achieving cell behavior control due to their exceptional photo-physical properties. Lanthanide-doped upconversion nanoparticles (UCNPs) have gained extensive attention as near-infrared (NIR)-responsive nanomaterials owing to excellent photostability, minimal tissue scattering, and especially anti-stokes ultraviolet (UV) as well as visible emissions, showing great potential in various applications.
Dual-Enhanced Raman Scattering-Based Characterization of Stem Cell Differentiation Using Graphene-Plasmonic Hybrid Nanoarray
DOI: https://doi.org/10.1021/acs.nanolett.9b03402
CORRESPONDENCE: Prof. Ki-Bum Lee (Rutgers University); Prof. Jeong-Woo Choi (Sogang University)
FIRST AUTHORS: Dr. Letao Yang (Rutgers University); Dr. Jin-Ho Lee (Rutgers University)
RESEARCH DESCRIPTION:
Surface-enhanced Raman scattering (SERS) has demonstrated great potential to analyze a variety of bio/chemical molecular interactions within cells in a highly sensitive and selective manner. Despite significant advancements, it remains a critical challenge to ensure high sensitivity and selectivity, while achieving uniform signal enhancement and high reproducibility for quantitative detection of targeted biomarkers within a complex stem cell microenvironment.
Nondestructive Characterization of Stem Cell Neurogenesis by a Magneto-Plasmonic Nanomaterial-Based Exosomal miRNA Detection
The full realization of stem cell-based treatments for neurodegenerative diseases requires precise control and characterization of stem cell fate. Recently, exosomes and their inner contents have been discovered to play critical roles in cell-cell interactions and intrinsic cellular regulations and have received wide attention as next-generation biomarkers. Moreover, exosomal microRNAs (miRNA) also offer an essential avenue for nondestructive molecular analyses of cell cytoplasm components.
New Technique Could Help Engineer Polluted Water Filter, Human Tissues
Rutgers-led team’s protein patterns look like flowers, trees, snowflakes
July 23, 2019
Scientists can turn proteins into never-ending patterns that look like flowers, trees or snowflakes, a technique that could help engineer a filter for tainted water and human tissues.
Their study, led by researchers at Rutgers University–New Brunswick, appears in the journal Nature Chemistry.
Winning Teams Design Systems to Convert Carbon Dioxide into Something Sweet
Congratulations Karin U. D. Calvinho and Anders Laursen on winning the initial phase of Nasa’s CO2 Conversion Challenge!
"The purpose of the challenge is to convert carbon dioxide into glucose in order to eventually create sugar-based fuel, food, medicines, adhesives and other products."
Biosensors: NIR Biosensing of Neurotransmitters in Stem Cell‐Derived Neural Interface Using Advanced Core–Shell Upconversion Nanoparticles
Neurotransmitters, for instance dopamine (DA), are significant endogenous signals in the central nervous system (CNS), as they play vital roles in modulating neurophysiological processes including cognition, emotion, memory, and other behaviors. Therefore, fast, ultra-sensitive, non-destructive and robust detection of neurotransmitters during stem cell differentiation and neuromodulation processes in the CNS would be of paramount importance for gaining an insight into how neural interactions regulate brain functions, developing better molecular diagnostics and therapeutics for neurological disorders. To this end, upconversion nanoparticles (UCNPs) have recently gained extensive attention as optical biosensors due to their excellent photo-stability, narrow emission bandwidths, as well as high signal to noise ratio, showing great potential in various applications; however, the relatively weak luminescence intensity due to low quantum efficiencies compromises the further development of UCNP-based applications.
Nondestructive Real-Time Monitoring of Enhanced Stem Cell Differentiation Using a Graphene-Au Hybrid Nanoelectrode Array
Stem cells have attracted increasing research interest in the field of regenerative medicine because of their unique ability to differentiate into multiple cell lineages. However, controlling stem cell differentiation efficiently and improving the current destructive characterization methods for monitoring stem cell differentiation are the critical issues.
Overcoming Chemoresistance in Cancer Using Nanotechnology-based Drug Delivery
Chemoresistance is a major challenge facing the effective treatment of cancers. To overcome resistance to chemotherapy, microRNA (miRNA), which are short (20−22 nucleotides) noncoding RNA molecules, has shown to be an attractive strategy. A growing body of evidence shows that modulation of miRNA levels in cancer can mitigate the development and progression of cancer.
A Biodegradable Hybrid Inorganic Nanoscaffold for Advanced Stem Cell Therapy
Considering the intrinsically limited regenerative capability of the central nervous system (CNS) and the complex inhibitory microenvironment of injured spinal cord, developing effective therapeutics for CNS diseases and injuries [e.g., Parkinson disease and spinal cord injury (SCI)] has been challenging. To this end, stem cell therapy can provide a promising solution. Neural stem cells can differentiate into neurons and restore the damaged neuronal circuits. Additionally, stem cells modulate the inhibitory microenvironment at the site of CNS disease and injury through the secretion of trophic factors. Nevertheless, the low survival rate and incomplete differentiation control of stem cells in vivo are critical barriers for the full realization of stem cell therapy potential. As such, there is an urgent need to develop an innovative approach to enhance stem cell transplantation and to control stem cell fate precisely.
Rutgers-led Research Could Revolutionize Nuclear Waste Reprocessing and Save Money
Seeking a better way to capture radioactive iodides in spent nuclear reactor fuel, Rutgers–New Brunswick scientists have developed an extremely efficient “molecular trap” that can be recycled and reused.
Computation-guided design of a stimulus-responsive multi-enzyme supramolecular assembly.
The construction of stimulus-responsive supramolecular complexes of metabolic pathway enzymes, inspired by natural multi-enzyme assemblies (metabolons), provides an attractive avenue for efficient and spatio-temporally controllable one-pot biotransformations.
