Targeted Polymersome Delivery of siRNA Induces Cell Death of Breast Cancer Cells Dependent upon Orai3 Protein Expression.
AuthorsPangburn TO, Georgiou K, Bates FS, Kokkoli E,
JournalLangmuir
PubMed ID22827285
Polymersomes, polymeric vesicles that self-assemble in aqueous solutions from block copolymers, have been avidly investigated in recent years as potential drug delivery agents. Past work has highlighted peptide-functionalized polymersomes as a highly promising targeted delivery system. However, few reports have investigated the ability of polymersomes to operate as gene delivery ... More
Identification and Characterization of Receptor-Specific Peptides for siRNA Delivery.
AuthorsRen Y, Hauert S, Lo JH, Bhatia SN,
JournalACS Nano
PubMed ID22909216
Tumor-targeted delivery of siRNA remains a major barrier in fully realizing the therapeutic potential of RNA interference. While cell-penetrating peptides (CPP) are promising siRNA carrier candidates, they are universal internalizers that lack cell-type specificity. Herein, we design and screen a library of tandem tumor-targeting and cell-penetrating peptides that condense siRNA ... More
Cell-permeable gomesin peptide promotes cell death by intracellular Ca(2+) overload.
AuthorsParedes-Gamero EJ, Casaes-Rodrigues RL, Moura GE, Domingues TM, Buri MV, Ferreira VH, Trindade ES, Moreno-Ortega AJ, Cano-Abad MF, Nader HB, Ferreira AT, Miranda A, Justo GZ, Tersariol IL,
JournalMol Pharm
PubMed ID22873645
In recent years, the antitumoral activity of antimicrobial peptides (AMPs) has been the goal of many research studies. Among AMPs, gomesin (Gm) displays antitumor activity by unknown mechanisms. Herein, we studied the cytotoxicity of Gm in the Chinese hamster ovary (CHO) cell line. Furthermore, we investigated the temporal ordering of ... More
Tear-mediated delivery of nanoparticles through transcytosis of the lacrimal gland.
AuthorsHsueh PY, Edman MC, Sun G, Shi P, Xu S, Lin YA, Cui H, Hamm-Alvarez SF, MacKay JA,
JournalJ Control Release
PubMed ID25523518
Rapid clearance from the tears presents a formidable obstacle to the delivery of peptide drugs to the eye surface. This impedes therapies for ocular infections, wound healing, and dry-eye disease that affect the vision of millions worldwide. To overcome this challenge, this manuscript explores a novel strategy to reach the ... More
A Rab11a-enriched subapical membrane compartment regulates a cytoskeleton-dependent transcytotic pathway in secretory epithelial cells of the lacrimal gland.
AuthorsXu S, Edman M, Kothawala MS, Sun G, Chiang L, Mircheff A, Zhu L, Okamoto C, Hamm-Alvarez S,
JournalJ Cell Sci
PubMed ID21984810
'Despite observations that the lacrimal gland has been identified as the principal source of dimeric immunoglobulin A (dIgA) in tears, the mechanism used by lacrimal gland acinar cells (LGACs) to transcytose dIgA produced by interstitial plasma cells is not well-characterized. This study identifies a transcytotic pathway in LGACs regulated by ... More
Oxidative stress protection by exogenous delivery of rhHsp70 chaperone to the retinal pigment epithelium (RPE), a possible therapeutic strategy against RPE degeneration.
AuthorsSubrizi A, Toropainen E, Ramsay E, Airaksinen AJ, Kaarniranta K, Urtti A,
Journal
PubMed ID25030185
'To measure the cytoprotective effects of rhHsp70 against oxidative stress and study its cellular uptake, intracellular and intraocular distribution in the retinal pigment epithelium. Human retinal pigment epithelial cells (ARPE-19) were pre-treated with rhHsp70 for 24 h, 48 h, and 72 h before being exposed to 1.25 mM hydrogen peroxide. Non-treated cells served as ... More
Visualizing the endocytosis of phenylephrine in living cells by quantum dot-based tracking.
AuthorsMa J, Wu L, Hou Z, Song Y, Wang L, Jiang W,
Journal
PubMed ID24855959
'To study the intracellular receptor-drug transportation, a fluorescent probe consisting of phenylephrine-polyethylene glycol-quantum dots conjugate was employed to track endocytosis process of phenylephrine in living cells. This type of movement was studied by continuously filming fluorescent images in the same cell. We also calculated the movement parameters, and divided the ... More
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
Nile Blue-based nanosized pH sensors for simultaneous far-red and near-infrared live bioimaging.
AuthorsMadsen J, Canton I, Warren NJ, Themistou E, Blanazs A, Ustbas B, Tian X, Pearson R, Battaglia G, Lewis AL, Armes SP,
Journal
PubMed ID24001153
'Diblock copolymer vesicles are tagged with pH-responsive Nile Blue-based labels and used as a new type of pH-responsive colorimetric/fluorescent biosensor for far-red and near-infrared imaging of live cells. The diblock copolymer vesicles described herein are based on poly(2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the biomimetic PMPC block is known to facilitate rapid ... 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
Live cell imaging of G protein-coupled receptors.
AuthorsTeichmann A, Schmidt A, Wiesner B, Oksche A, Schülein R,
JournalMethods Mol Biol
PubMed ID22674164
Live cell imaging experiments with G protein-coupled receptors (GPCRs) tagged with fluorescent fusion proteins were originally performed to study trafficking and subcellular location of these important drug targets. In the past decade, however, substantial progress came from improved imaging methods and from the cloning of novel fluorescent fusion proteins. Today, ... More
Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes.
AuthorsDandekar P, Jain R, Keil M, Loretz B, Muijs L, Schneider M, Auerbach D, Jung G, Lehr CM, Wenz G,
JournalJ Control Release
PubMed ID22789529
Cationic polyrotaxanes, obtained by temperature activated threading of cationic cyclodextrin derivatives onto water-soluble cationic polymers (ionenes), form metastable nanometric polyplexes with pDNA and combinations of siRNA with pDNA. Because of their low toxicity, the polyrotaxane polyplexes constitute a very interesting system for the transfection of polynucleotides into mammalian cells. The ... More
Myosin 1E coordinates actin assembly and cargo trafficking during clathrin-mediated endocytosis.
AuthorsCheng J, Grassart A, Drubin DG,
JournalMol Biol Cell
PubMed ID22675027
Myosin 1E (Myo1E) is recruited to sites of clathrin-mediated endocytosis coincident with a burst of actin assembly. The recruitment dynamics and lifetime of Myo1E are similar to those of tagged actin polymerization regulatory proteins. Like inhibition of actin assembly, depletion of Myo1E causes reduced transferrin endocytosis and a significant delay ... More
Intracellular dynamics and fate of polystyrene nanoparticles in A549 Lung epithelial cells monitored by image (cross-) correlation spectroscopy and single particle tracking.
AuthorsDeville S, Penjweini R, Smisdom N, Notelaers K, Nelissen I, Hooyberghs J, Ameloot M,
Journal
PubMed ID26164626
Novel insights in nanoparticle (NP) uptake routes of cells, their intracellular trafficking and subcellular targeting can be obtained through the investigation of their temporal and spatial behavior. In this work, we present the application of image (cross-) correlation spectroscopy (IC(C)S) and single particle tracking (SPT) to monitor the intracellular dynamics ... More
PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking.
AuthorsGao Y, Li Y, Li Y, Yuan L, Zhou Y, Li J, Zhao L, Zhang C, Li X, Liu Y,
Journal
PubMed ID25419788
The cytotoxicity of chemotherapeutic agents to healthy organs and drug resistance of tumor cells are believed to be the main obstacles to the successful cancer chemotherapy in the clinic. To ensure that anticancer drugs could be delivered to the tumor region, are quickly released from carriers in tumor cells and ... More
LRRTM3 interacts with APP and BACE1 and has variants associating with late-onset Alzheimer's disease (LOAD).
AuthorsLincoln S, Allen M, Cox CL, Walker LP, Malphrus K, Qiu Y, Nguyen T, Rowley C, Kouri N, Crook J, Pankratz VS, Younkin S, Younkin L, Carrasquillo M, Zou F, Abdul-Hay SO, Springer W, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Lewis JM, Dickson D, Graff-Radford NR, Petersen RC, Eckman E, Younkin SG, Ertekin-Taner N,
Journal
PubMed ID23750206
Leucine rich repeat transmembrane protein 3 (LRRTM3) is member of a synaptic protein family. LRRTM3 is a nested gene within a-T catenin (CTNNA3) and resides at the linkage peak for late-onset Alzheimer's disease (LOAD) risk and plasma amyloid ß (Aß) levels. In-vitro knock-down of LRRTM3 was previously shown to decrease ... More
Probing site-exclusive binding of aqueous QDs and their organelle-dependent dynamics in live cells by single molecule spectroscopy.
AuthorsDong C, Chowdhury B, Irudayaraj J,
JournalAnalyst
PubMed ID23493749
Understanding the biophysical and chemical interactions of nanoprobes and their fate upon entering live cells is critical for developing fundamental insights related to intracellular diagnostics, drug delivery and targeting. In this article we report herein a single molecule analysis procedure to quantitate site-specific exclusive membrane binding of N-acetyl-L-cysteine (NAC)-capped cadmium ... More
Fluorescent peptide-PNA chimeras for imaging monoamine oxidase A mRNA in neuronal cells.
AuthorsSethi D, Chen CP, Jing RY, Thakur ML, Wickstrom E,
JournalBioconjug Chem
PubMed ID22239616
Monoamine oxidases (MAO) catalyze the oxidative deamination of many biogenic amines and are integral proteins found in the mitochondrial outer membrane. Changes in MAO-A levels are associated with depression, trait aggression, and addiction. Here we report the synthesis, characterization, and in vitro evaluation of novel fluorescent peptide-peptide nucleic acid (PNA) ... More
Overcoming endosomal barrier by amphotericin B-loaded dual pH-responsive PDMA-b-PDPA micelleplexes for siRNA delivery.
AuthorsYu H, Zou Y, Wang Y, Huang X, Huang G, Sumer BD, Boothman DA, Gao J,
JournalACS Nano
PubMed ID22011045
The endosomal barrier is a major bottleneck for the effective intracellular delivery of siRNA by nonviral nanocarriers. Here, we report a novel amphotericin B (AmB)-loaded, dual pH-responsive micelleplex platform for siRNA delivery. Micelles were self-assembled from poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) (PDMA-b-PDPA) diblock copolymers. At pH 7.4, AmB was loaded into the ... More
PEGylated liposomal doxorubicin targeted to a5ß1-expressing MDA-MB-231 breast cancer cells.
AuthorsShroff K, Kokkoli E,
JournalLangmuir
PubMed ID22268611
Targeting drugs selectively to cancer cells can potentially benefit cancer patients by avoiding side effects generally associated with several cancer therapies. One of the attractive approaches to direct the drug cargo to specific sites is to incorporate ligands at the surface of the delivery systems. Integrin a(5)ß(1) is overexpressed in ... More
Immunobiotic lactic acid bacteria beneficially regulate immune response triggered by poly(I:C) in porcine intestinal epithelial cells.
AuthorsHosoya S, Villena J, Shimazu T, Tohno M, Fujie H, Chiba E, Shimosato T, Aso H, Suda Y, Kawai Y, Saito T, Alvarez S, Ikegami S, Itoh H, Kitazawa H,
JournalVet Res
PubMed ID22046952
ABSTRACT: This study analyzed the functional expression of TLR3 in various gastrointestinal tissues from adult swine and shows that TLR3 is expressed preferentially in intestinal epithelial cells (IEC), CD172a+CD11R1high and CD4+ cells from ileal Peyer's patches. We characterized the inflammatory immune response triggered by TLR3 activation in a clonal porcine ... 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
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
Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform.
Authors
JournalElife
PubMed ID31451149
Enhanced penetrative siRNA delivery by a nanodiamond drug delivery platform against hepatocellular carcinoma 3D models.
Authors
JournalNanoscale
PubMed ID34542130
Regulation of extracellular matrix degradation and metastatic spread by IQGAP1 through endothelin-1 receptor signalling in ovarian cancer.
AuthorsChellini L, Caprara V, Spadaro F, Sestito R, Bagnato A, Rosanò L
JournalMatrix Biol
PubMed ID30367951
'The invasive phenotype of serous ovarian cancer (SOC) cells is linked to the formation of actin-based protrusions, invadopodia, operating extracellular matrix (ECM) degradation and metastatic spread. Growth factor receptors might cause engagement of integrin-related proteins, like the polarity protein IQ-domain GTPase-activating protein 1 (IQGAP1), to F-actin core needed for invadopodia ... More
Targeted Delivery of Deoxycytidine Kinase to Her2-Positive Cells Enhances the Efficacy of the Nucleoside Analog Fludarabine.
AuthorsKoduvayur SP, Su Y, Kay BK, Lavie A,
JournalPLoS One
PubMed ID27280468
'Cytotoxic drugs, such as nucleoside analogs and toxins, commonly suffer from off-target effects. One approach to mitigate this problem is to deliver the cytotoxic drug selectively to the intended site. While for toxins this can be achieved by conjugating the cell-killing moiety to a targeting moiety, it is not an ... More
Immuno-potentiating pathway of HBsAg-HBIG immunogenic complex visualized.
AuthorsLiu H, Geng S, Wang B, Wu B, Xie X, Wang S, Zhong Y, Wang X, Qu D, Wen Y, Wang B,
JournalHum Vaccin Immunother
PubMed ID26618396
'Chronic viral hepatitis B (CHB) is a major global health problem. A therapeutic vaccine for CHB comprised of yeast-derived recombinant HBsAg-anti-HBs immunogenic complexes (YIC) has been devloped by us. A series of clinical trials has shown its therapeutic efficacy in decreasing HBV viral load and converting serum HBeAg-positive to anti-HBe-positive ... More
Modification of the in vitro uptake mechanism and antioxidant levels in HaCaT cells and resultant changes to toxicity and oxidative stress of G4 and G6 poly(amidoamine) dendrimer nanoparticles.
AuthorsMaher MA, Byrne HJ,
JournalAnal Bioanal Chem
PubMed ID27209595
'The mechanism of cellular uptake by endocytosis and subsequent oxidative stress has been identified as the paradigm for the toxic response of cationically surface charged nanoparticles. In an attempt to circumvent the process, the effect of increased cellular membrane permeability on the uptake mechanisms of poly(amidoamine) dendrimers generations 4 (G4) ... More
Transmembrane 4 L Six Family Member 5 Senses Arginine for mTORC1 Signaling.
Authors
JournalCell Metab
PubMed ID30956113
Utilization of HEPES for Enhancing Protein Transfection into Mammalian Cells.
Authors
JournalMol Ther Methods Clin Dev
PubMed ID30740472
Dysregulation of mannose-6-phosphate-dependent cholesterol homeostasis in acinar cells mediates pancreatitis.
Authors
JournalJ Clin Invest
PubMed ID34128834
The Establishment and Application Studies on Precise Lysosome pH Indicator Based on Self-Decomposable Nanoparticles.
Authors
JournalNanoscale Res Lett
PubMed ID32642882
The epithelial polarity regulator LGALS9/galectin-9 induces fatal frustrated autophagy in KRAS mutant colon carcinoma that depends on elevated basal autophagic flux.
Authors
JournalAutophagy
PubMed ID26086204
Mitochondrial copper depletion suppresses triple-negative breast cancer in mice.
Authors
JournalNat Biotechnol
PubMed ID33077961
Binding, internalization and fate of Huntingtin Exon1 fibrillar assemblies in mitotic and nonmitotic neuroblastoma cells.
The aggregation of Huntingtin (HTT) protein and of its moiety encoded by its Exon1 (HTTExon1) into fibrillar structures inside neurons is the molecular hallmark of Huntington's disease. Prion-like transmission of these aggregates between cells has been demonstrated. The cell-to-cell transmission mechanisms of these protein aggregates and the susceptibility of different ... More
Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis.
AuthorsDaynac M, Chouchane M, Collins HY, Murphy NE, Andor N, Niu J, Fancy SPJ, Stallcup WB, Petritsch CK
JournalNat Commun
PubMed ID30131568
Oligodendrocyte progenitor cells (OPC) undergo asymmetric cell division (ACD) to generate one OPC and one differentiating oligodendrocyte (OL) progeny. Loss of pro-mitotic proteoglycan and OPC marker NG2 in the OL progeny is the earliest immunophenotypic change of unknown mechanism that indicates differentiation commitment. Here, we report that expression of the ... More
Spatial regulation of GPR64/ADGRG2 signaling by ß-arrestins and GPCR kinases.
AuthorsAzimzadeh P, Talamantez-Lyburn SC, Chang KT, Inoue A, Balenga N
JournalAnn N Y Acad Sci
PubMed ID31502283
Mechanisms of activation, signaling, and trafficking of adhesion G protein-coupled receptors (aGPCRs) have remained largely unknown. Several aGPCRs, including GPR56/ADGRG1 and GPR64/ADGRG2, show increased activity in the absence of their N-terminal fragment (NTF). This constitutive signaling is plausibly caused by the binding of extracellular N-terminal 15-25 amino acid-long tethered agonist ... More
Intracellular localization of polymyxins in human alveolar epithelial cells.
AuthorsAhmed MU, Velkov T, Zhou QT, Fulcher AJ, Callaghan J, Zhou F, Chan K, Azad MAK, Li J
JournalJ Antimicrob Chemother
PubMed ID30357331
Current inhaled polymyxin therapy is empirical and often large doses are administered, which can lead to pulmonary adverse effects. There is a dearth of information on the mechanisms of polymyxin-induced lung toxicity and their intracellular localization in lung epithelial cells. ... More