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https://www.readbyqxmd.com/read/29908938/microfluidic-self-assembly-of-a-combinatorial-library-of-single-and-dual-ligand-liposomes-for-in-vitro-and-in-vivo-tumor-targeting
#1
Rui Ran, Haofei Wang, Yun Liu, Yue Hui, Qi Sun, Arjun Seth, David Wibowo, Dong Chen, Chun-Xia Zhao
Precise engineering of nanoparticles with systematically varied properties (size, charge surface properties, targeting ligands, etc.) remains a challenge, limiting the effective optimization of nanoparticles for particular applications. Herein we report a single-step microfluidic combinatorial approach for producing a library of single and dual-ligand liposomes with systematically-varied properties including size, zeta potential, targeting ligand, ligand density, and ligand ratio. A targeting ligand folic acid and a cell penetrating peptide TAT were employed to achieve the optimal synergistic targeting effect...
June 14, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29907765/dual-functional-peptide-with-defective-interfering-genes-effectively-protects-mice-against-avian-and-seasonal-influenza
#2
Hanjun Zhao, Kelvin K W To, Hin Chu, Qiulu Ding, Xiaoyu Zhao, Cun Li, Huiping Shuai, Shuofeng Yuan, Jie Zhou, Kin-Hang Kok, Shibo Jiang, Kwok-Yung Yuen
Limited efficacy of current antivirals and antiviral-resistant mutations impairs anti-influenza treatment. Here, we evaluate the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Viral replication is significantly reduced in cell lines transfected with DIG-3. Mice treated with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus, respectively, have significantly better survivals (80% and 50%) than control mice (0%). We further develop a dual-functional peptide TAT-P1, which delivers DIG-3 with high efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification...
June 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29904274/evaluation-of-the-bioactivity-of-a-mastoparan-peptide-from-wasp-venom-and-of-its-analogues-designed-through-targeted-engineering
#3
Xiaoling Chen, Luyao Zhang, Yue Wu, Lei Wang, Chengbang Ma, Xinping Xi, Olaf R P Bininda-Emonds, Chris Shaw, Tianbao Chen, Mei Zhou
Mastoparan is a typical cationic and amphipathic tetradecapeptide found in wasp venom and exhibits potent biological activities. Yet, compared with other insect-derived peptides, such as melittin from the bee venom, this family have been underrated. Herein, we evaluated the biological activities of mastoparan-C (MP-C), which was identified from the venom of the European Hornet ( Vespa crabro ), and rationally designed two analogues (a skeleton-based cyclization by two cysteine residues and an N-terminal extension via tat-linked) for enhancing the stability of the biological activity and membrane permeability, respectively...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29894162/nuclear-targeted-photothermal-therapy-prevents-cancer-recurrence-with-near-infrared-triggered-copper-sulfide-nanoparticles
#4
Na Li, Qiaoqiao Sun, Zhengze Yu, Xiaonan Gao, Wei Pan, Xiuyan Wan, Bo Tang
Clinical cancer treatments nowadays still face the challenge of recurrence due to the residual cancer cells and minute lesions in surgeries or chemotherapies. To effectively address the problem, we introduce a strategy for constructing cancer cell nuclear-targeted copper sulfide nanoparticles (NPs) with significant photothermal effect to completely kill residual cancer cells and prevent local cancer recurrence. The NPs could directly target to the tumor cells and further enter the nucleus by the surface modification of RGD and TAT peptides...
June 12, 2018: ACS Nano
https://www.readbyqxmd.com/read/29880393/enhanced-radiosensitization-of-human-glioblastoma-multiforme-cells-with-phosphorylated-peptides-derived-from-gli2
#5
Lizhang Han, Ling Tang, Zheng Jiang, Yuquan Jiang
Glioma-Associated Oncogene Family Zinc Finger 2 (Gli2) seems to be the major nuclear effector of Sonic Hedgehog (SHH) signaling to regulate self-renewal and tumorigenic potential of Glioblastoma multiforme (GBM) cells. Three phosphorylated peptides derived from Gli2 were synthesized and combined with cell-penetrating peptide Tat-(47-57) (AYGRKKRRQRRR). Western Blot was applied to detect the phosphorylation level of Gli2 and cell division protein kinase 6 (CDK6) luciferase reporter was utilized to detect the transcriptional activator function of Gli2...
May 30, 2018: Neuropeptides
https://www.readbyqxmd.com/read/29847726/cell-penetrating-peptide-patchy-deformable-polymeric-nanovehicles-with-enhanced-cellular-uptake-and-transdermal-delivery
#6
Daehwan Park, Jin Yong Lee, Heui Kyoung Cho, Woo Jin Hong, Jisun Kim, Hyemyung Seo, Ikjang Choi, Youngbok Lee, Juhyeon Kim, Sun-Joon Min, So-Hyun Yoon, Jae Sung Hwang, Kwang Jin Cho, Jin Woong Kim
We herein propose a polymeric nanovehicle system that has the ability to remarkably improve cellular uptake and transdermal delivery. Cell-penetrating peptide-patchy deformable polymeric nanovehicles were fabricated by tailored co-assembly of amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL), mannosylerythritol lipid (MEL), and YGRKKRRQRRR-Cysteamine (TAT)-linked MEL. Using X-ray diffraction, differential scanning calorimetry, and nuclear magnetic resonance analyses, we revealed that the incorporation of MEL having an asymmetric alkyl chain configuration, was responsible for the deformable phase property of the vehicles...
May 30, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29847471/inhibition-of-the-ubc9-e2-sumo-conjugating-enzyme-crmp2-interaction-decreases-nav1-7-currents-and-reverses-experimental-neuropathic-pain
#7
Liberty François-Moutal, Erik T Dustrude, Yue Wang, Tatiana Brustovetsky, Angie Dorame, Weina Ju, Aubin Moutal, Samantha Perez-Miller, Nickolay Brustovetsky, Vijay Gokhale, May Khanna, Rajesh Khanna
We previously reported that destruction of the small ubiquitin-like modifier (SUMO) modification site in the axonal collapsin response mediator protein 2 (CRMP2) was sufficient to selectively decrease trafficking of the voltage-gated sodium channel NaV1.7 and reverse neuropathic pain. Here, we further interrogate the biophysical nature of the interaction between CRMP2 and the SUMOylation machiner affinity between CRMP2 and Ubc9. A heptamer peptide harboring CRMP2's SUMO motif, also bound with similar affinity to Ubc9 and disrupted the CRMP2-Ubc9 interaction in a concentration-dependent manner...
May 25, 2018: Pain
https://www.readbyqxmd.com/read/29780163/heteromerization-of-%C3%AE-opioid-receptor-and-cholecystokinin-b-receptor-through-the-third-transmembrane-domain-of-the-%C3%AE-opioid-receptor-contributes-to-the-anti-opioid-effects-of-cholecystokinin-octapeptide
#8
Yin Yang, Qian Li, Qi-Hua He, Ji-Sheng Han, Li Su, You Wan
Activation of the cholecystokinin type B receptor (CCKBR) by cholecystokinin octapeptide (CCK-8) inhibits opioid analgesia. Chronic opiate treatment leads to an increase in the CCK-8 concentration and thus enhances the antagonism of CCK-8 against opioid analgesia; the underlying molecular mechanisms remain of great interest. In the present study, we validated the colocalization of the μ-opioid receptor (MOR) and CCKBR in pain signal transmission-related spinal cord dorsal horn and dorsal root ganglion neurons of rats...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29769639/a-novel-cell-penetrating-peptide-protects-against-neuron-apoptosis-after-cerebral-ischemia-by-inhibiting-the-nuclear-translocation-of-annexin-a1
#9
Xing Li, Lu Zheng, Qian Xia, Lu Liu, Meng Mao, Huijuan Zhou, Yin Zhao, Jing Shi
Nuclear translocation of annexin A1 (ANXA1) has recently been reported to participate in neuronal apoptosis after cerebral ischemia. Prevention of the nuclear translocation of ANXA1 should therefore inhibit neuronal apoptosis and protect against cerebral stroke. Here, we found that, in the repeat III domain of ANXA1, the amino-acid residues from R228 to F237 function as a unique nuclear translocation signal (NTS) and are required for nuclear translocation of ANXA1. Intriguingly, we synthesized a cell-penetrating peptide derived by conjugating the trans-activator of transcription (Tat) domain to the NTS sequence...
May 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29742341/luminescence-tunable-polynorbornenes-for-simultaneous-multicolor-imaging-in-subcellular-organelles
#10
Nan Xie, Ke Feng, Jianqun Shao, Bin Chen, Chen-Ho Tung, Li-Zhu Wu
Through modular ROMP (ring-opening metathesis polymerization), biofunctional polynorbornenes are designed and fabricated from panchromatic fluorophores, bioactive peptides and PEG solubilizer for organelle-specific multicolor imaging. Attributed to the free permutation and combination of highly fluorescent red rhodamine B, green dichlorofluorescein and blue 9,10-diphenylanthracene fluorophores as well as signaling peptide sequences of Fx rFx K and TAT, we successfully realize simultaneous multicolor imaging toward lysosomes and mitochondria in living cells firstly utilizing polymeric scaffolds...
May 9, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29738954/antibacterial-and-anti-tb-tat-peptidomimetics-with-improved-efficacy-and-half-life
#11
Govind S Bhosle, Laxman Nawale, Amar M Yeware, Dhiman Sarkar, Moneesha Fernandes
Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid...
April 30, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29734017/identification-of-a-cell-penetrating-peptide-applicable-to-a-protein-based-transcription-activator-like-effector-expression-system-for-cell-engineering
#12
Tomoki Takashina, Takayoshi Koyama, Satoshi Nohara, Masakatsu Hasegawa, Akira Ishiguro, Kenta Iijima, Jun Lu, Mari Shimura, Tadashi Okamura, Tetsushi Sakuma, Takashi Yamamoto, Yukihito Ishizaka
Cellular reprogramming is a promising technology in regenerative medicine, but most studies have been performed by using expression vectors. For future clinical applications, it is necessary to establish a system in which cell engineering can be manipulated without any risk of damaging the genome. Here, we identified a cell-penetrating peptide composed of 10 amino acids (RIFIHFRIGC) with nuclear trafficking activity and found that it was significantly more potent than a Tat-derived peptide or polyarginine peptide (R11)...
August 2018: Biomaterials
https://www.readbyqxmd.com/read/29733971/ph-sensitive-nanoparticles-as-smart-carriers-for-selective-intracellular-drug-delivery-to-tumor
#13
Xin-Xin Li, Jing Chen, Jian-Min Shen, Ran Zhuang, Shi-Qi Zhang, Zi-Yun Zhu, Jing-Bo Ma
Herein, a smart pH-sensitive nanoparticle (DGL-PEG-Tat-KK-DMA-DOX) was prepared to achieve the selective intracellular drug delivery. In this nanoparticle, a PEG-grafted cell penetrating peptide (PEG-Tat-KK) was designed and acted as the cell penetrating segment. By introducing the pH-sensitive amide bonds between the peptide and blocking agent (2,3-dimethylmaleic anhydride, DMA), the controllable moiety (PEG-Tat-KK-DMA) endowed the nanoparticle with a charge-switchable shell and temporarily blocked penetrating function, thus improving the specific internalization...
May 4, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29730306/empty-turnip-yellow-mosaic-virus-capsids-as-delivery-vehicles-to-mammalian-cells
#14
Doyeong Kim, Younghee Lee, Theo W Dreher, Tae-Ju Cho
Turnip yellow mosaic virus (TYMV) was able to enter animal cells when the spherical plant virus was conjugated with Tat, a cell penetrating peptide (CPP). Tat was chemically attached to the surface lysine residues of TYMV using hydrazone chemistry. Baby hamster kidney (BHK) cells were incubated with either unmodified or Tat-conjugated TYMV and examined by flow cytometry and confocal microscopic analyses. Tat conjugation was shown to be more efficient than Lipofectamine in allowing TYMV to enter the mammalian cells...
May 3, 2018: Virus Research
https://www.readbyqxmd.com/read/29728138/hiv-1-tat-alters-neuronal-intrinsic-excitability
#15
Walter Francesconi, Fulvia Berton, Maria Cecilia G Marcondes
OBJECTIVE: In HIV+ individuals, the virus enters the central nervous system and invades innate immune cells, producing important changes that result in neurological deficits. We aimed to determine whether HIV plays a direct role in neuronal excitability. Of the HIV peptides, Tat is secreted and acts in other cells. In order to examine whether the HIV Tat can modify neuronal excitability, we exposed primary murine hippocampal neurons to that peptide, and tested its effects on the intrinsic membrane properties, 4 and 24 h after exposure...
May 4, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29722179/co-administration-of-kla-tat-peptide-and-irgd-to-enhance-the-permeability-on-a549-3d-multiple-sphere-cells-and-accumulation-on-xenograft-mice
#16
Cuihua Hu, Xiaolong Chen, Yibing Huang, Yuxin Chen
To enhance the anticancer activity, tumor penetration ability of the hybrid anticancer peptide, in this study, a TAT (RKKRRQRRR) peptide modified kla peptide (KLAKLAKKLAKLAK, with all D-amino acids), named kla-TAT, was co-administrated with the homing/penetrating peptide iRGD which could enhance the permeability of chemical drug in solid tumor and tumor vessel by co-administration. In this study, the non-small cell lung cancer (NSCLC) A549 cell line with the iRGD targeting receptor neuropilin-1 (NRP-1) high expression was selected to establish the 2D monolayer cell, 3D multiple cell spheroids and xenograft mice model...
May 2, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29717122/therapeutic-potential-of-a-phospholipase-d1-inhibitory-peptide-fused-with-a-cell-penetrating-peptide-as-a-novel-anti-asthmatic-drug-in-a-der-f-2-induced-airway-inflammation-model
#17
Yun Young Lee, So Young Lee, Shin-Young Park, Hye-Jin Choi, Eung-Gook Kim, Joong-Soo Han
Asthma is a chronic lung disease that causes airflow obstruction due to airway inflammation. However, its therapeutics remain inadequate. We previously reported that phospholipase D1 (PLD1) is a key enzyme involved in the production of pro-inflammatory cytokines in airway inflammation induced by the house dust mite allergen Dermatophagoides farinae 2 (Der f 2). We also revealed that PLD1 is specifically inactivated by AP180 (assembly protein, 180 kDa) and identified the PLD1-specific binding motif (TVTSP) of AP180...
May 1, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29713715/combining-autophagy-inducing-peptides-and-brefeldin-a-delivered-by-perinuclear-localized-mesoporous-silica-nanoparticles-a-manipulation-strategy-for-er-phagy
#18
Yimin Wang, Zhao Zhao, Fujing Wei, Zewei Luo, Yixiang Duan
Autophagic degradation of the endoplasmic reticulum (ER-phagy) has been found to play a critical role in human sensory neuropathy. So far, however, specific and efficient intervention means for ER-phagy remain unexplored. Herein, brefeldin A (BFA), a blocking agent on protein transport between the ER and Golgi, was screened from ER stress inducers. BFA was then delivered to the perinuclear area co-localized with the ER by a mesoporous silica nanoparticle-based drug-carrier functionalized with autophagy-inducing peptides of TAT-beclin 1 (MSNs-BFA), to evoke a perturbation of ER-phagy...
May 10, 2018: Nanoscale
https://www.readbyqxmd.com/read/29688120/conjugates-of-tat-and-folate-with-dox-loaded-chitosan-micelles-offer-effective-intracellular-delivery-ability
#19
Shengyu Zhang, Yanjun Liu, Ye Gan, Nanqing Qiu, Yueqing Gu, Hongyan Zhu
The key for better antitumor efficacy is to improve the specificity of antitumor drugs for tumor cells and diminish their cytotoxicity to normal tissues. Targeted nanoparticles as antitumor drug delivery system can resolve this problem. In this study, we prepared folate and TAT (arginine-rich cell-penetrating peptide) modified N-PEG-N'-octyl-chitosan to form the folate/TAT-PEG-OC micelles. Then, the molecular structure, morphology, size distribution and bio-safety of the micelles were characterized. In order to investigate the drug-loading capacity of folate/TAT-PEG-OC micelles, doxorubicin (DOX) was used as model drug to prepare DOX-loaded chitosan micelles...
June 13, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29683209/inhibition-of-astroglial-connexin43-hemichannels-with-tat-gap19-exerts-anticonvulsant-effects-in-rodents
#20
Laura Walrave, Anouk Pierre, Giulia Albertini, Najat Aourz, Dimitri De Bundel, Ann Van Eeckhaut, Mathieu Vinken, Christian Giaume, Luc Leybaert, Ilse Smolders
Accumulating evidence shows a key function for astrocytic connexin43 (Cx43) signaling in epilepsy. However, the lack of experimental distinction between Cx43 gap junction channels (GJCs) and hemichannels (HCs) has impeded the identification of the exact contribution of either channel configurations to epilepsy. We therefore investigated whether TAT-Gap19, a Cx mimetic peptide that inhibits Cx43 HCs but not the corresponding Cx43 GJCs, influences experimentally induced seizures in rodents. Dye uptake experiments in acute hippocampal slices of mice demonstrated that astroglial Cx43 HCs open in response to the chemoconvulsant pilocarpine and this was inhibited by TAT-Gap19...
April 23, 2018: Glia
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