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Targeted drug delivery

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https://www.readbyqxmd.com/read/28545160/-99m-tc-labeled-ngr-chlorambucil-conjugate-99m-tc-hynic-clb-c-ngr-for-targeted-chemotherapy-and-molecular-imaging
#1
Kusum Vats, Drishty Satpati, Rohit Sharma, Chandan Kumar, Haladhar D Sarma, Ashutosh Dash
Targeted delivery of chemotherapeutic drug at the tumor site enhances the efficacy with minimum systemic exposure. Towards this drugs conjugated with peptides having affinity towards a particular molecular target are recognized as affective agents for targeted chemotherapy. Thus in the present study tumor homing NGR peptide ligand was conjugated to DNA alkylating nitrogen mustard, chlorambucil (CLB). The peptide drug conjugate (PDC), CLB-c(NGR) was radiolabeled with (99m) Tc-HYNIC core to trace its pharmacokinetics and biodistribution pattern...
May 25, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28544965/nrgd-modified-lycobetaine-and-octreotide-combination-delivery-system-to-overcome-multiple-barriers-and-enhance-anti-glioma-efficacy
#2
Tijia Chen, Xu Song, Ting Gong, Yao Fu, Liuqing Yang, Zhirong Zhang, Tao Gong
For glioma as one of the most common and lethal primary brain tumors, the presence of BBB, BBTB, vasculogenic mimicry (VM) channels and tumor-associated macrophages (TAMs) are key biological barriers. Here, a novel drug delivery system which could efficiently deliver drugs to glioma by overcoming multi-barriers and increase antitumor efficacy through multi-therapeutic mechanisms was well developed. In this study, a multi-target peptide nRGD was used to transport across the BBB, mediate tumor penetration and target TAMs...
May 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28544521/oral-nucleic-acid-therapy-using-multicompartmental-delivery-systems
#3
REVIEW
Husain Attarwala, Murui Han, Jonghan Kim, Mansoor Amiji
Nucleic acid-based therapeutics has the potential for treating numerous diseases by correcting abnormal expression of specific genes. Lack of safe and efficacious delivery strategies poses a major obstacle limiting clinical advancement of nucleic acid therapeutics. Oral route of drug administration has greater delivery challenges, because the administered genes or oligonucleotides have to bypass degrading environment of the gastrointestinal (GI) tract in addition to overcoming other cellular barriers preventing nucleic acid delivery...
May 24, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28544466/simultaneous-imaging-of-endogenous-survivin-mrna-and-on-demand-drug-release-in-live-cells-by-using-a-mesoporous-silica-nanoquencher
#4
Peiyan Yuan, Xin Mao, Kok Chan Chong, Jiaqi Fu, Sijun Pan, Shuizhu Wu, Changmin Yu, Shao Q Yao
The design of multifunctional drug delivery systems capable of simultaneous target detection, imaging, and therapeutics in live mammalian cells is critical for biomedical research. In this study, by using mesoporous silica nanoparticles (MSNs) chemically modified with a small-molecule dark quencher, followed by sequential drug encapsulation, MSN capping with a dye-labeled antisense oligonucleotide, and bioorthogonal surface modification with cell-penetrating poly(disulfide)s, the authors have successfully developed the first mesoporous silica nanoquencher (qMSN), characterized by high drug-loading and endocytosis-independent cell uptake, which is able to quantitatively image endogenous survivin mRNA and release the loaded drug in a manner that depends on the survivin expression level in tumor cells...
May 24, 2017: Small
https://www.readbyqxmd.com/read/28544324/albumin-templated-manganese-dioxide-nanoparticles-for-enhanced-radioisotope-therapy
#5
Longlong Tian, Qian Chen, Xuan Yi, Jiawen Chen, Chao Liang, Yu Chao, Kai Yang, Zhuang Liu
Although nanoparticle-based drug delivery systems have been widely explored for tumor-targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia-associated resistance to radiation-induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide (131) I labeled human serum albumin (HSA)-bound manganese dioxide nanoparticles ((131) I-HSA-MnO2 ) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME)...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28543738/crispr-editing-in-biological-and-biomedical-investigation
#6
Xing-Da Ju, Jing Xu, Zhong Sheng Sun
The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR--associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542623/gallium-nanoparticles-facilitate-phagosome-maturation-and-inhibit-growth-of-virulent-mycobacterium-tuberculosis-in-macrophages
#7
Seoung-Ryoung Choi, Bradley E Britigan, David M Moran, Prabagaran Narayanasamy
New treatments and novel drugs are required to counter the growing problem of drug-resistant strains of Mycobacterium tuberculosis (M.tb). Our approach against drug resistant M.tb, as well as other intracellular pathogens, is by targeted drug delivery using nanoformulations of drugs already in use, as well as drugs in development. Among the latter are gallium (III) (Ga)-based compounds. In the current work, six different types of Ga and rifampin nanoparticles were prepared in such a way as to enhance targeting of M...
2017: PloS One
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#8
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542563/evaluation-of-somatostatin-and-nucleolin-receptors-for-therapeutic-delivery-in-non-small-cell-lung-cancer-stem-cells-applying-the-somatostatin-analog-dotatate-and-the-nucleolin-targeting-aptamer-as1411
#9
Sif Holmboe, Pernille Lund Hansen, Helge Thisgaard, Ines Block, Carolin Müller, Niels Langkjær, Poul Flemming Høilund-Carlsen, Birgitte Brinkmann Olsen, Jan Mollenhauer
Cancer stem cells represent the putative tumor-driving subpopulation thought to account for drug resistance, relapse, and metastatic spread of epithelial and other cancer types. Accordingly, cell surface markers for therapeutic delivery to cancer stem cells are subject of intense research. Somatostatin receptor 2 and nucleolin are known to be overexpressed by various cancer types, which have elicited comprehensive efforts to explore their therapeutic utilization. Here, we evaluated somatostatin receptor 2 targeting and nucleolin targeting for therapeutic delivery to cancer stem cells from lung cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28542423/plasmid-free-crispr-cas9-genome-editing-in-plasmodium-falciparum-confirms-mutations-conferring-resistance-to-the-dihydroisoquinolone-clinical-candidate-sj733
#10
Emily D Crawford, Jenai Quan, Jeremy A Horst, Daniel Ebert, Wesley Wu, Joseph L DeRisi
Genetic manipulation of the deadly malaria parasite Plasmodium falciparum remains challenging, but the rise of CRISPR/Cas9-based genome editing tools is increasing the feasibility of altering this parasite's genome in order to study its biology. Of particular interest is the investigation of drug targets and drug resistance mechanisms, which have major implications for fighting malaria. We present a new method for introducing drug resistance mutations in P. falciparum without the use of plasmids or the need for cloning homologous recombination templates...
2017: PloS One
https://www.readbyqxmd.com/read/28542292/development-of-a-versatile-oncolytic-virus-platform-for-local-intra-tumoural-expression-of-therapeutic-transgenes
#11
Nalini Marino, Sam Illingworth, Prithvi Kodialbail, Ashvin Patel, Hugo Calderon, Rochelle Lear, Kerry D Fisher, Brian R Champion, Alice C N Brown
Oncolytic viruses which infect and kill tumour cells can also be genetically modified to express therapeutic genes that augment their anti-cancer activities. Modifying oncolytic viruses to produce effective cancer therapies is challenging as encoding transgenes often attenuates virus activity or prevents systemic delivery in patients due to the risk of off-target expression of transgenes in healthy tissues. To overcome these issues we aimed to generate a readily modifiable virus platform using the oncolytic adenovirus, enadenotucirev...
2017: PloS One
https://www.readbyqxmd.com/read/28542038/hypoxia-as-a-target-for-drug-combination-therapy-of-liver-cancer
#12
Cressida Bowyer, Andrew L Lewis, Andrew W Lloyd, Gary J Phillips, Wendy M Macfarlane
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths worldwide. The standard of care for intermediate HCC is transarterial chemoembolization, which combines tumour embolization with locoregional delivery of the chemotherapeutic doxorubicin. Embolization therapies induce hypoxia, leading to the escape and proliferation of hypoxia-adapted cancer cells. The transcription factor that orchestrates responses to hypoxia is hypoxia-inducible factor 1 (HIF-1). The aim of this work is to show that targeting HIF-1 with combined drug therapy presents an opportunity for improving outcomes for HCC treatment...
May 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28541681/platelet-microcapsule-hybrids-leverage-contractile-force-for-targeted-delivery-of-hemostatic-agents
#13
Caroline E Hansen, David R Myers, Wallace Hunter Baldwin, Yumiko Sakurai, Shannon L Meeks, L Andrew Lyon, Wilbur A Lam
We report a cell-mediated, targeted drug delivery system utilizing polyelectrolyte multilayer capsules that hybridize with the patient's own platelets upon intravenous administration. The hybridized platelets function as the sensor and actuator for targeted drug delivery and controlled release in our system. These capsules are biochemically and mechanically tuned to enable platelet adhesion and capsule rupture upon platelet activation and contraction, enabling the targeted and controlled "burst" release of an encapsulated biotherapeutic...
May 25, 2017: ACS Nano
https://www.readbyqxmd.com/read/28541524/metal-bound-clamp-tag-inhibits-proteolytic-cleavage
#14
Michaela L McNiff, Jennifer S Chadwick
Biologics can be an improvement to small molecule drugs, providing high specificity for an identified target, lowering toxicity and limiting side effects. To achieve effective delivery, the biologic must have sufficient time to reach the target tissue. A prolonged half-life in the circulating environment is desired, but often serum stability is limited by proteases. Proteolysis in the serum causes degradation and inactivation as the biologic is fragmented and more rapidly cleared from the body. To improve the circulating half-life, large, hydrophilic polymers may be conjugated or stable fusion tags may be engineered to increase the effective size of the peptide and to hinder degradation by proteases...
May 25, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28540828/tumor-tissue-transport-after-intraperitoneal-anticancer-drug-delivery
#15
Charlotte Carlier, Ada Mathys, Emiel De Jaeghere, Margo Steuperaert, Olivier De Wever, Wim Ceelen
Intraperitoneal (IP) drug delivery, either as an intraoperative chemoperfusion or as adjuvant, repeated instillation, is an established treatment modality in patients with peritoneal carcinomatosis. The efficacy of IP drugs depends on its ability to penetrate the tumor stroma in order to reach their (sub)cellular target. It is known, that drug penetration after IP delivery is limited to a few millimeters. Here, we review the basic tissue transport mechanisms after IP delivery, and discuss the biophysical barriers and obstacles that limit penetration distance...
March 28, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28540814/lyso-thermosensitive-liposomal-doxorubicin-for-treatment-of-bladder-cancer
#16
Andrew S Mikhail, Ayele H Negussie, William F Pritchard, Dieter Haemmerich, David Woods, Ivane Bakhutashvili, Juan Esparza-Trujillo, Sam J Brancato, John Karanian, Piyush K Agarwal, Bradford J Wood
PURPOSE: To evaluate lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox(®)) in combination with loco-regional mild hyperthermia (HT) for targeted drug delivery to the bladder wall and potential treatment of bladder cancer. MATERIAL AND METHODS: Porcine in vivo studies were performed with the following groups: (i) intravenous (IV) LTLD with hyperthermia (LTLD + HT); (ii) IV doxorubicin (DOX) with hyperthermia (IV DOX + HT) and (iii) IV LTLD without hyperthermia (LTLD - HT)...
May 10, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28540812/galectin-1-based-tumour-targeting-for-gold-nanostructure-mediated-photothermal-therapy
#17
Samir V Jenkins, Dmitry A Nedosekin, Emily K Miller, Vladimir P Zharov, Ruud P M Dings, Jingyi Chen, Robert J Griffin
PURPOSE: To demonstrate delivery of Au nanocages to cells using the galectin-1 binding peptide anginex (Ax) and to demonstrate the value of this targeting for selective in vitro photothermal cell killing. MATERIALS AND METHODS: Au nanocages were synthesised, coated with polydopamine (PDA), and conjugated with Ax. Tumour and endothelial cell viability was measured with and without laser irradiation. Photoacoustic (PA) mapping and PA flow cytometry were used to confirm cell targeting in vitro and in tissue slices ex vivo...
May 9, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28540720/specifically-increased-paclitaxel-release-in-tumor-and-synergetic-therapy-by-a-hyaluronic-acid-tocopherol-nanomicelle
#18
Hanbo Zhang, Wei Li, Xiaomeng Guo, Fenfen Kong, Zuhua Wang, Chunqi Zhu, Lihua Luo, Qingpo Li, Jie Yang, Yongzhong Du, Jian You
Recently, interest in tumor-targeting and site-specific drug release from nanoparticles as a means of drug delivery has increased. In this study, we reported on a smart nanosized micelle formed by hyaluronic acid (HA) conjugated with D-α-Tocopherol Succinate (TOS) using a disulfide bond as the linker (HA-SS-TOS, HSST). HSST micelles can specifically bind to the CD44 receptors that are overexpressed on cancer cells. The high levels of glutathione (GSH) in tumor cells selectively break the disulfide bond linker...
May 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28540717/imaging-laser-triggered-drug-release-from-gold-nanocages-with-transient-absorption-lifetime-microscopy-talm
#19
Yongkui Xu, Qi Liu, Ruoyu He, Xianchong Miao, Minbiao Ji
Nanoparticles have shown promise in loading and delivering drugs for targeted therapy. Many progresses have been made in the design, synthesis and modification of nanoparticles to fulfill such goals. However, realizing targeted intracellular delivery and controlled release of drugs remain challenging, partly due to the lack of reliable tools to detect the drug releasing process. In this paper, we applied femtosecond laser pulses to trigger the explosion of gold nanocages (AuNCs) and controlled the intracellular release of loaded AlPcS molecules for photodynamic therapy (PDT)...
May 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28539887/biomaterials-for-local-controlled-drug-delivery-to-the-injured-spinal-cord
#20
REVIEW
Alexis M Ziemba, Ryan J Gilbert
Affecting approximately 17,000 new people each year, spinal cord injury (SCI) is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI...
2017: Frontiers in Pharmacology
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