A5050727391- Supramolecular Self-Assembly in Materials
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Spectroscopy Techniques in Biomedical and Chemical Research
- Lipid Membrane Structure and Behavior
- Nanoplatforms for cancer theranostics
- Glycosylation and Glycoproteins Research
- ATP Synthase and ATPases Research
- Thermography and Photoacoustic Techniques
- Polydiacetylene-based materials and applications
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Photochromic and Fluorescence Chemistry
- Advanced Fluorescence Microscopy Techniques
- Antimicrobial Peptides and Activities
- Ubiquitin and proteasome pathways
- Photoacoustic and Ultrasonic Imaging
- Silk-based biomaterials and applications
- Peptidase Inhibition and Analysis
- Metabolomics and Mass Spectrometry Studies
- Alkaline Phosphatase Research Studies
- Advanced Chemical Sensor Technologies
- Bone Tissue Engineering Materials
Boston University
2023-2025
Brandeis University
2016-2025
Shanghai Tenth People's Hospital
2016
Tongji University
2014-2016
Rice University
2002
Tsinghua University
2002
Most of the reported mitochondria-targeting molecules are lipophilic and cationic, thus they may become cytotoxic with accumulation. Here we show enzymatic cleavage branched peptides that carry negative charges for targeting mitochondria. Conjugating a well-established protein tag (i.e., FLAG-tag) to self-assembling motifs affords precursors form micelles. Enzymatic hydrophilic FLAG motif (DDDDK) by enterokinase (ENTK) turns micelles nanofibers. After being taken up cells, micelles, upon...
Changing an oxygen atom of the phosphoester bond in phosphopeptides by a sulfur enables instantly targeting Golgi apparatus (GA) and selectively killing cancer cells enzymatic self-assembly. Specifically, conjugating cysteamine S-phosphate to C-terminal self-assembling peptide generates thiophosphopeptide. Being substrate alkaline phosphatase (ALP), thiophosphopeptide undergoes rapid ALP-catalyzed dephosphorylation form thiopeptide that self-assembles. The enters via caveolin-mediated...
Herein, we show that an enzymatic reaction can generate peptide assemblies sequestrate proteins to selectively kill cancer cells. A phosphopeptide bearing the antagonistic motif (AVPI) inhibitors of apoptotic (IAPs) enters cells and normal by caveolin-dependent endocytosis macropinocytosis, respectively. The AVPI-bearing sequestrates IAPs releases bortezomib (BTZ), a proteasome inhibitor, in cytosol cells, but rescues (namely, HS-5 cells) trafficking BTZ into lysosomes. Alkaline phosphatase...
Emerging evidence indicates that mitochondria contribute to drug resistance in cancer, but how selectively target the of cancer cells remains less explored. Here, we show perimitochondrial enzymatic self-assembly for targeting liver cells. Nanoparticles a peptide–lipid conjugate, being substrate enterokinase (ENTK), encapsulate chloramphenicol (CLRP), clinically used antibiotic is deactivated by glucuronidases cytosol not mitochondria. Perimitochondrial ENTK cleaves Flag-tag on conjugate...
Tumorigenic risk of undifferentiated human induced pluripotent stem cells (iPSCs), being a major obstacle for clinical application iPSCs, requires novel approaches selectively eliminating iPSCs. Here, we show that an l-phosphopentapeptide, upon the dephosphorylation catalyzed by alkaline phosphatase (ALP) overexpressed rapidly forms intranuclear peptide assemblies made α-helices to kill The phosphopentapeptide, consisting four l-leucine residues and C-terminal l-phosphotyrosine,...
Herein, we show intranuclear nanoribbons formed upon dephosphorylation of leucine-rich L- or D-phosphopeptide catalyzed by alkaline phosphatase (ALP) to selectively kill osteosarcoma cells. Being dephosphorylated ALP, the peptides are first transformed into micelles and then converted nanoribbons. The peptides/assemblies aggregate on cell membranes, enter cells via endocytosis, finally accumulate in nuclei (mainly nucleoli). Proteomics analysis suggests that assemblies interact with histone...
By optically sensing absorption-induced photothermal effect, mid-infrared (IR) (MIP) microscope enables super-resolution IR imaging of biological systems in water. However, the speed current sample-scanning MIP system is limited to milliseconds per pixel, which insufficient for capturing living dynamics. detecting transient signal induced by a single pulse through fast digitization, we report laser-scanning that increases three orders magnitude. To realize single-pulse detection, use...
Abstract Instructed-assembly (iAssembly or iA) refers to the formation of ordered superstructures molecules as consequence at least one trigger event (e.g., a reaction ligand-receptor interaction). As biomimetic process that transforms from an equilibrium another equilibrium, iA is emerging powerful approach provide spatiotemporal control for range potential biomedical applications, including molecular imaging, cancer therapy, and tissue engineering. This account introduces general concept...
Presently, little is known of how the inter-organelle crosstalk impacts cancer cells owing to lack approaches that can manipulate communication in cells. We found a negatively charged, enzyme cleavable peptide (MitoFlag) enables trafficking histone protein H2B, nuclear protein, mitochondria MitoFlag interacts with location sequence H2B block it from entering nucleus. A protease on cleaves Flag MitoFlag/H2B complex form assemblies retain and facilitate mitochondria. Adding NLS, replacing...
A new strategy for creating enzyme-responsive hydrogels by employing an N-hydroxyimide–heparin conjugate, designed to act as both enzyme-mediated radical initiator and enzyme-sensitive therapeutic carrier, is described. novel redox initiation system involving glucose oxidase (GOx), conjugate reported. The GOx-mediated polymerization reaction allows quick formation of under mild conditions, with excellent flexibility in the modulation physical chemical characteristics. heparin-specific...
Selectively targeting the endoplasmic reticulum (ER) of cancer cells, though promising a new strategy for therapy, remains underdeveloped. Enzyme-instructed self-assembly (EISA) is emerging as approach selectively ER cells. This work reports an easily accessible branched peptide that consists D-tetrapeptide backbone and branch with sequence KYDKKKKDG (K: lysine; Y: tyrosine; D: aspratic acid; G: glycine), being EISA substrate typsin-1 (PRSS1), inhibits Depending on type level PRSS1...
Recent studies have demonstrated that enzyme-instructed self-assembly (EISA) in extra- or intracellular environments can serve as a multistep process for controlling cell fate. There is little knowledge, however, about the kinetics of EISA complex around cells. Here, we design and synthesize three dipeptidic precursors (ld-1-SO3, dl-1-SO3, dd-1-SO3), consisting diphenylalanine (l-Phe-d-Phe, d-Phe-l-Phe, d-Phe-d-Phe, respectively) backbone, which are capped by 2-(naphthalen-2-yl)acetic acid...
Alkaline phosphatase (ALP) enables intracellular targeting by peptide assemblies, but how the ALP substrates enter cells remains elusive. Here we show that nanoscale phosphopeptide assemblies cluster to enable caveolae-mediated endocytosis (CME) and endosomal escape. Specifically, fluorescent phosphopeptides undergo enzyme-catalyzed self-assembly form nanofibers. Live cell imaging unveils nanoparticles, coincubated with HEK293 overexpressing red protein-tagged tissue-nonspecific (TNAP-RFP),...
Despite their critical role in context-dependent interactions for protein functions, intrinsically disordered regions (IDRs) are often overlooked designing peptide assemblies. Here, we exploit IDRs to enable heterotypic assemblies of peptides, where "context-dependent" refers assembly behavior driven by with other molecules. By attaching an aromatic segment oppositely charged achieve a nanofiber formation. Although the same-charged peptides cannot self-assemble, form nanofibers. Cryo-EM...
The use of protease (<italic>e.g.</italic>, enterokinase) to cut branched peptides generates supramolecular hydrogels, opening a new way explore soft materials for biomedicine.
Abstract Targeting immunosuppressive metastatic cancer cells is a key challenge in therapy. We recently have shown that rigid‐rod aromatic, pBP−NBD, responds to enzymes and kill osteosarcoma (mOS) castration resistant prostate (CRPC) mimetic bone microenvironment. However, pBP−NBD demonstrated moderate efficacy against CRPC cells. To enhance activity, we incorporated the unnatural amino acid L‐ or D‐4,4′‐biphenylalanine (L‐ D−BiP) into drastically increasing cellular uptake inhibition....
Real-time tracking of intracellular carbohydrates remains challenging. While click chemistry allows bio-orthogonal tagging with fluorescent probes, the reaction permanently alters target molecule and only a single snapshot. Here, we demonstrate click-free mid-infrared photothermal (MIP) imaging azide-tagged in live cells. Leveraging micromolar detection sensitivity for 6-azido-trehalose (TreAz) 300-nm spatial resolution MIP imaging, trehalose recycling pathway mycobacteria, from cytoplasmic...
Since mitochondria contribute to tumorigenesis and drug resistance in cancer, mitochondrial genetic engineering promises a new direction for cancer therapy. Here, we report the use of perimitochondrial enzymatic noncovalent synthesis (ENS) peptides delivering genes selectively into cells engineering. Specifically, micelles bind voltage-dependent anion channel (VDAC) on proteolysis by enterokinase (ENTK), generating nanofibers cells. This process, facilitating selective delivery nucleic acid...