Dynamic colocalization microscopy to characterize intracellular trafficking of nanomedicines.
AuthorsVercauteren D, Deschout H, Remaut K, Engbersen JF, Jones AT, Demeester J, De Smedt SC, Braeckmans K,
JournalACS Nano
PubMed ID21923168
'To gain a better understanding of intracellular processing of nanomedicines, we employed quantitative live-cell fluorescence colocalization microscopy to study endosomal trafficking of polyplexes in retinal pigment epithelium cells. A new, dynamic colocalization algorithm was developed, based on particle tracking and trajectory correlation, allowing for spatiotemporal characterization of internalized polyplexes in ... More
Polycations such as polyethylenimine (PEI) are used in many novel nonviral vector designs and there are continuous efforts to increase our mechanistic understanding of their interactions with cells. Even so, the mechanism of polyplex escape from the endosomal/lysosomal pathway after internalization is still elusive. The ... More
Inhibitors of intravesicular acidification protect against Shiga toxin in a pH-independent manner.
AuthorsDyve Lingelem AB, Bergan J, Sandvig K,
JournalTraffic
PubMed ID22132807
Shiga toxin inhibits protein synthesis after being transported from the cell surface to endosomes and retrogradely through the Golgi apparatus to the endoplasmic reticulum (ER) and into the cytosol. In this study, we have abolished proton gradients across internal membranes in different ways and investigated the effect on the various ... More
Effective endogenous gene silencing mediated by pH responsive peptides proceeds via multiple pathways.
AuthorsLam JK, Liang W, Lan Y, Chaudhuri P, Chow MY, Witt K, Kudsiova L, Mason AJ,
JournalJ Control Release
PubMed ID22138072
Cationic amphipathic histidine rich peptides possess high plasmid DNA and siRNA delivery capabilities. To further understand the pH responsive siRNA delivery process and evaluate the capabilities of such peptides we have investigated their ability to mediate specific silencing of endogenous GAPDH gene activity in MCF-7 and A549 cells and compared ... More
Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics.
AuthorsMarrache S, Dhar S,
JournalProc Natl Acad Sci U S A
PubMed ID22991470
Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric nanoparticle (NP) system and its optimization for efficient delivery of various ... More
Distribution and dynamics of Lamp1-containing endocytic organelles in fibroblasts deficient in BLOC-3.
Late endosomes and lysosomes of mammalian cells in interphase tend to concentrate in the perinuclear region that harbors the microtubule-organizing center. We have previously reported abnormal distribution of these organelles - as judged by reduced percentages of cells displaying pronounced perinuclear accumulation - in mutant fibroblasts lacking BLOC-3 (for ;biogenesis ... More
Fluorescence lifetime imaging unravels C. trachomatis metabolism and its crosstalk with the host cell.
AuthorsSzaszák M, Steven P, Shima K, Orzekowsky-Schröder R, Hüttmann G, König IR, Solbach W, Rupp J,
JournalPLoS Pathog
PubMed ID21779161
Chlamydia trachomatis is an obligate intracellular bacterium that alternates between two metabolically different developmental forms. We performed fluorescence lifetime imaging (FLIM) of the metabolic coenzymes, reduced nicotinamide adenine dinucleotides [NAD(P)H], by two-photon microscopy for separate analysis of host and pathogen metabolism during intracellular chlamydial infections. NAD(P)H autofluorescence was detected inside ... More
Spreading of neurodegenerative pathology via neuron-to-neuron transmission of ß-amyloid.
Alzheimer's disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of ß-amyloid (Aß) plaques, which are the other histological hallmark of AD, does ... More
Baculovirus-mediated gene transfer into mammalian cells.
AuthorsBoyce FM, Bucher NL,
JournalProc Natl Acad Sci U S A
PubMed ID8637876
This paper describes the use of the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) as a vector for gene delivery into mammalian cells. A modified AcMNPV virus was prepared that carried the Escherichia coli lacZ reporter gene under control of the Rous sarcoma virus promoter and mammalian RNA processing ... More
BacMam technology and its application to drug discovery.
AuthorsAmes RS, Kost TA, Condreay JP,
JournalExpert Opin Drug Discov
PubMed ID23488908
The recombinant baculovirus/insect cell system was firmly established as a leading method for recombinant protein production when a new potential use for these viruses was revealed in 1995. It was reported that engineered recombinant baculoviruses could deliver functional expression cassettes to mammalian cell types; a system which has come to ... More
Tools and techniques to measure mitophagy using fluorescence microscopy.
AuthorsDolman NJ, Chambers KM, Mandavilli B, Batchelor RH, Janes MS,
Journal
PubMed ID24121704
Mitophagy is a specialized form of autophagy that removes damaged mitochondria, thereby maintaining efficient cellular metabolism and reducing cellular stress caused by aberrant oxidative bursts. Deficits in mitophagy underlie several diseases, and a substantial body of research has elucidated key steps in the pathways that lead to and execute autophagic ... More
Cellular uptake of cyclotide MCoTI-I follows multiple endocytic pathways.
Cyclotides are plant-derived proteins that naturally exhibit various biological activities and whose unique cyclic structure makes them remarkably stable and resistant to denaturation or degradation. These attributes, among others, make them ideally suited for use as drug development tools. This study investigated the cellular uptake of cyclotide, MCoTI-I in live ... More
Glycan sulfation patterns define autophagy flux at axon tip via PTPRs-cortactin axis.
AuthorsSakamoto K, Ozaki T, Ko YC, Tsai CF, Gong Y, Morozumi M, Ishikawa Y, Uchimura K, Nadanaka S, Kitagawa H, Zulueta MML, Bandaru A, Tamura JI, Hung SC, Kadomatsu K
JournalNat Chem Biol
PubMed ID31061498
'Chondroitin sulfate (CS) and heparan sulfate (HS) are glycosaminoglycans that both bind the receptor-type protein tyrosine phosphatase PTPRs, affecting axonal regeneration. CS inhibits axonal growth, while HS promotes it. Here, we have prepared a library of HS octasaccharides and, together with synthetic CS oligomers, we found that PTPRs preferentially interacts ... More
Fundc1 is necessary for proper body axis formation during embryogenesis in zebrafish.
AuthorsXu G, Shen H, Nibona E, Wu K, Ke X, Al Hafiz MA, Liang X, Zhong X, Zhou Q, Qi C, Zhao H
JournalSci Rep
PubMed ID31827208
'FUN14 domain-containing protein 1 (FUNDC1) is a mitochondrial outer membrane protein which is responsible for hypoxia-induced mitophagy in mammalian cells. Knockdown of fundc1 is known to cause severe defects in the body axis of a rare minnow. To understand the role of Fundc1 in embryogenesis, we used zebrafish in this ... More
Targeted Delivery of C/EBPα-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC.
Authors
JournalMol Ther Nucleic Acids
PubMed ID31546149
Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release.
Authors
JournalOncotarget
PubMed ID27329722
The lack of functional DNMT2/TRDMT1 gene modulates cancer cell responses during drug-induced senescence.
Authors
JournalAging (Albany NY)
PubMed ID34139673
Synthesis of marmycin A and investigation into its cellular activity.
Authors
JournalNat Chem
PubMed ID26291947
Nerve bundle formation during the promotion of peripheral nerve regeneration: collagen VI-neural cell adhesion molecule 1 interaction.
Authors
JournalNeural Regen Res
PubMed ID34558529
Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction.
Authors
JournalJ Biol Chem
PubMed ID26527686
Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A.
Authors
JournalNat Commun
PubMed ID30918259
Dysregulation of mitochondria-lysosome contacts by GBA1 dysfunction in dopaminergic neuronal models of Parkinson's disease.
Authors
JournalNat Commun
PubMed ID33753743
Transit and integration of extracellular mitochondria in human heart cells.
Authors
JournalSci Rep
PubMed ID29234096
Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus.
AuthorsVo MT, Smith BJ, Nicholas J, Choi YB
JournalNat Commun
PubMed ID31324791
Viral control of mitochondrial quality and content has emerged as an important mechanism for counteracting the host response to virus infection. Despite the knowledge of this crucial function of some viruses, little is known about how herpesviruses regulate mitochondrial homeostasis during infection. Human herpesvirus 8 (HHV-8) is an oncogenic virus ... More
Antibody-Drug Conjugate Using Ionized Cys-Linker-MMAE as the Potent Payload Shows Optimal Therapeutic Safety.
AuthorsWang Y, Liu L, Fan S, Xiao D, Xie F, Li W, Zhong W, Zhou X
JournalCancers (Basel)
PubMed ID32245171
Monomethyl auristatin E (MMAE) is the most popular and widely used cytotoxin in the development of antibody-drug conjugates (ADCs). However, current MMAE-based ADCs are all constructed using cleavable linkers, and this design concept still has insurmountable drawbacks. Their potential instabilities and lipophilic MMAE-induced "bystander effect" inevitably increase the toxicity to ... More
Biological response and cytotoxicity induced by lipid nanocapsules.
AuthorsSzwed M, Torgersen ML, Kumari RV, Yadava SK, Pust S, Iversen TG, Skotland T, Giri J, Sandvig K
JournalJ Nanobiotechnology
PubMed ID31907052
Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of ... More