Array-Based Protein Sensing Using an Aggregation-Induced Emission (AIE) Light-Up Probe

Protein detection and identification are important for the diagnosis of diseases; however, the development of facile sensing probes still remains challenging. Here, we present an array-based "turn on" protein-sensing platform capable of detecting and identifying proteins using aggregation-induced emission luminogens (AIEgens). The water-soluble AIEgens in which fluorescence was initially turned off showed strong fluorescence in the presence of nanomolar concentrations of proteins via restriction of the intramolecular rotation of the AIEgens. The binding affinities between the AIEgens and proteins were associated with various chemical functional groups on AIEgens, resulting in distinct fluorescent-signal outcomes for each protein. The combined fluorescence outputs provided sufficient information to detect and discriminate proteins of interest by linear discriminant analysis. Furthermore, the array-based sensor enabled classification of different concentrations of specific proteins. These results provide novel insight into the use of the AIEgens as a new type of sensing probe in array-based systems

Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper-Hollow Silica Nanoparticles

Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment.ope

Single-cell transcriptome of the mouse retinal pigment epithelium in response to a low-dose of doxorubicin

Single cell transcriptomics pinpoints a cell subpopulation that could be involved in inducing cellular senescence of the retinal pigment epithelium, which in turn may construe retinal degenerative disease. Cellular senescence of the retinal pigment epithelium (RPE) is thought to play an important role in vision-threatening retinal degenerative diseases, such as age-related macular degeneration (AMD). However, the single-cell RNA profiles of control RPE tissue and RPE tissue exhibiting cellular senescence are not well known. We have analyzed the single-cell transcriptomes of control mice and mice with low-dose doxorubicin (Dox)-induced RPE senescence (Dox-RPE). Our results have identified 4 main subpopulations in the control RPE that exhibit heterogeneous biological activities and play roles in ATP synthesis, cell mobility/differentiation, mRNA processing, and catalytic activity. In Dox-RPE mice, cellular senescence mainly occurs in the specific cluster, which has been characterized by catalytic activity in the control RPE. Furthermore, in the Dox-RPE mice, 6 genes that have not previously been associated with senescence also show altered expression in 4 clusters. Our results might serve as a useful reference for the study of control and senescent RPE

Engineering surface functionality of gold nanoparticles for therapeutic applications

Over the past few decades, tremendous efforts have been made to develop nanomaterials for biotechnological applications such as therapeutics. Understanding and engineering interfaces between biomacromolecules and nanomaterials is a key to the creation of successful therapeutic systems. My research has been oriented toward developing therapeutic systems using gold nanoparticles (AuNPs) incorporating material science, organic synthesis, and biology. For this purpose, mixed monolayer protected AuNPs (∼2 nm core size) with various functional groups have been employed for triggering therapeutic effects. Several strategies have been accomplished using anticancer drugs that non-covalently and covalently incorporate onto AuNPs as a drug delivery carrier. Alternatively, AuNPs were developed by regulating host-guest complexation processes inside the cell, allowing control of the therapeutic effect of the AuNP. In addition, by using host-guest chemical events on the AuNPs, exocytosis of the AuNPs was controlled, enabling their prolonged retention inside of the cells, providing new strategies for improving conventional drug delivery systems. Therefore, engineering of the AuNP surface can afford new pathways for designing and improving therapeutics

Intra-Mitochondrial Biomineralization for Inducing Apoptosis of Cancer Cells

Biomineralization is an essential physiological process, which efficiently utilizes inorganic elements available in body fluids. It involves in homeostasis of bones and skeletal tissues for maintaining mechanical function. Especially, sequestration and secretion of intracellular mineral deposits contributes to regulation of cellular fate. Recently, extracellular biomineralization has been studied in vitro and in vivo level as potential cancer treatment. However, abnormal extracellular mineral deposits can cause damage to normal cells near the mineral nucleation sites, and the loss of cellular susceptibility to environmental changes. To overcome this drawbacks, we proposed intracellular biomineralization targeting mitochondria. Inside cancerous mitochondria, accumulated selectively of inorganic element and basic condition provided effective condition to form biominerals. The resulting biominerals might induce depolarization of mitochondria membrane potential, leading to dysfunction of mitochondria. In turn, the dysfunction resulted in apoptosis. This intra-mitochondrial biomineralization would provide a new tool for regulating cellular functions and potential therapeutic applications

Array-based Protein Sensing using an Aggregation Induced Emission Light-Up Probe

Protein detection and identification is important for diagnosis of diseases but the development of facile sensing probes still remains challenging. Herein, we present an array-based ???turn on??? protein sensing platform that can detect and identify proteins using aggregation induced emission luminogens (AIEgens). The water-soluble AIEgens that the fluorescence are initially turned-off, showed strong fluorescence in the presence of nanomolar concentration of proteins via the restriction of the intramolecular rotation (RIR) of the AIEgens. The binding affinities between the AIEgens and proteins were associated with various chemical functional groups on AIEgens, resulting in the distinct fluorescent signal outcomes for each protein. The combining fluorescence outputs provided sufficient information to detect and discriminate proteins of interest by linear discriminant analysis (LDA). Furthermore, the array-based sensor could be used to classify different concentration of specific proteins. This study provides a new sight into the use of the AIEgens as a new type of sensing probe installable in an array-based system

Cytotoxicity of Gold Nanoparticles Associates with Multivalent Interactions at Interface

Design and synthesis of nanomaterials for biomedical application continues to receive immense interest among the researcher. Among various nanoparticles, gold nanoparticles have recently garnered great attention for biomedical applications (e.g., diagnostic and therapeutic applications) because of their unique fundamental properties. Gold nanoparticles are mostly used for drug delivery due to their non-toxic and biocompatible nature. Here, we have designed hydrophobic gold nanoparticles, which show cytotoxicity to cancer cells as well multidrug resistance cancer cell and induce apoptosis to cancer cell by ROS generation. Moreover, this hydrophobic gold nanoparticles also inhibit the spheroid growth. This finding will help in consideration of toxicity during the design of gold nanoparticles for drug delivery application