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https://www.readbyqxmd.com/read/28817371/phase-i-ii-trial-of-labetuzumab-govitecan-anti-ceacam5-sn-38-antibody-drug-conjugate-in-patients-with-refractory-or-relapsing-metastatic-colorectal-cancer
#1
Efrat Dotan, Steven J Cohen, Alexander N Starodub, Christopher H Lieu, Wells A Messersmith, Pamela S Simpson, Michael J Guarino, John L Marshall, Richard M Goldberg, J Randolph Hecht, William A Wegener, Robert M Sharkey, Serengulam V Govindan, David M Goldenberg, Jordan D Berlin
Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28816449/paralog-specificity-determines-subcellular-distribution-action-mechanism-and-anticancer-activity-of-trap1-inhibitors
#2
Hye-Kyung Park, Hanbin Jeong, Eunhwa Ko, Geumwoo Lee, Ji-Eun Lee, Sang Kwang Lee, An-Jung Lee, Jin Young Im, Sung Hu, Seong Heon Kim, Ji Hoon Lee, Changwook Lee, Soosung Kang, Byoung Heon Kang
Although Hsp90 inhibitors can inhibit multiple tumorigenic pathways in cancer cells, their anticancer activity has been disappointingly modest. However, by forcing Hsp90 inhibitors into the mitochondria with mitochondrial delivery vehicles, they were converted into potent drugs targeting the mitochondrial Hsp90 paralog TRAP1. Here, to improve mitochondrial drug accumulation without using the mitochondrial delivery vehicle, we increased freely available drug concentrations in the cytoplasm by reducing the binding of the drugs to the abundant cytoplasmic Hsp90...
August 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28816384/intracellular-delivery-of-functional-native-antibodies-under-hypoxic-conditions-by-using-a-biodegradable-silica-nanoquencher
#3
Shao Q Yao, Peiyan Yuan, Hailong Zhang, Linghui Qian, Xin Mao, Shubo Du, Changmin Yu, Bo Peng
Antibodies are important biopharmaceuticals, but almost all antibody-based drugs are limited to targeting antigens located at the cell exterior due to their inability to enter the cell interior. Available methods for intracellular delivery of antibodies have major shortcomings. Herein we report an approach to encapsulate native antibodies in a biodegradable silica nanoquencher (BS-qNP) which could undergo efficient cellular uptake and intracellular degradation to release antibodies under hypoxic conditions...
August 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28815766/preparation-of-robust-metal-free-magnetic-nanoemulsions-encapsulating-low-molecular-weight-nitroxide-radicals-and-hydrophobic-drugs-directed-toward-mri-visible-targeted-delivery
#4
Rui Tamura, Kota Nagura, Yusa Takemoto, Satori Moronaga, Yoshiaki Uchida, Satoshi Shimono, Akihiko Shiino, Kenji Tanigaki, Tsukuru Amano, Fumi Yoshino, Yohei Noda, Satoshi Koizumi, Naoki Komatsu, Tatsuhisa Kato, Jun Yamauchi
With a view to developing a theranostic nanomedicine for magnetic resonance (MR) imaging-visible targeted drug delivery system, robust metal-free magnetic nanoemulsions (mean particle sizes of less than 20 nm) consisting of the biocompatible surfactant 1 and the incorporated hydrophobic low-molecular-weight 2,2,5-trimethyl-5-(4-alkoxy)phenylpyrrolidine-N-oxyl radicals [(±)-2] have been prepared in pH 7.4 phosphate-buffered saline. The structure of the nanoemulsions has been characterized by electron paramagnetic resonance spectroscopy, and dynamic light scattering and small angle neutron scattering measurements...
August 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28815721/rgd-peptide-based-target-drug-delivery-of-doxorubicin-nanomedicine
#5
Yuan Sun, Chen Kang, Fei Liu, You Zhou, Lei Luo, Hongzhi Qiao
Preclinical Research Doxorubicin (DOX) is commonly used for the treatment of breast cancer and lymphoma. However, its clinical use has been severely limited due to cardiotoxicity, requiring the development of safer and more efficient pharmaceutical formulations of DOX. Advances in nanotechnology have provided new ways to administer chemotherapeutic drugs like DOX are conveyed into the body and to tumor sites. These Nanotechnology approaches have aided in the selective accumulation of DOX into tumor sites via the enhanced permeability and retention...
August 16, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28814832/combinatorial-and-sequential-delivery-of-gemcitabine-and-oseltamivir-phosphate-from-implantable-poly-d-l-lactic-co-glycolic-acid-cylinders-disables-human-pancreatic-cancer-cell-survival
#6
Stephanie Allison Logan, Amanda J Brissenden, Myron R Szewczuk, Ronald J Neufeld
Combination therapies against multiple targets are currently being developed to prevent resistance to a single chemotherapeutic agent and to extirpate pre-existing resistance in heterogeneous cancer cells in tumors due to selective pressure from the single agent. Gemcitabine (GEM), a chemotherapeutic agent, is the current standard of care for patients with pancreatic cancer. Patients with pancreatic cancer receiving GEM have a low progression-free survival. Given the poor response rate to GEM, cancer cells are known to develop rapid resistance to this drug...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814310/modelling-the-benefits-of-long-acting-or-transmission-blocking-drugs-for-reducing-plasmodium-falciparum-transmission-by-case-management-or-by-mass-treatment
#7
Michael T Bretscher, Jamie T Griffin, Azra C Ghani, Lucy C Okell
BACKGROUND: Anti-malarial drugs are an important tool for malaria control and elimination. Alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. Different compounds potentially have different impacts on transmission-with some providing periods of prolonged chemoprophylaxis whilst others have greater transmission-blocking potential. The aim was to quantify the relative benefit of such properties for transmission reduction to inform target product profiles in the drug development process and choice of first-line anti-malarial treatment in different endemic settings...
August 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28814163/protease-activated-nanomaterials-for-targeted-cancer-theranostics
#8
Yung-Chieh Chan, Michael Hsiao
Cancer metastasis accompanies irreversible proteolysis. Malignant cells that abnormally express extracellular proteases usually lead to a poor outcome during cancer progression. The development of protease-activated drugs is an important goal. Moreover, the specific proteolytic mechanism can be used as a diagnostic strategy. Currently, nanotechnology for use in medication has been extensively developed to exploit the physical and chemical properties of nanoparticles. For example, to improve the efficacy of cancer therapy drugs, targeted delivery has been attempted by combining a targeting ligand with a nanoparticle...
August 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28814080/drug-delivery-from-a-multi-faceted-ultrasound-contrast-agent-influence-of-shell-composition
#9
Lauren J Jablonowski, Nutte T Teraphongphom, Margaret A Wheatley
Many cancer therapy regimes still rely heavily on the systemic administration of toxic chemotherapeutic agents. Ultrasound contrast agents consisting of microbubbles (MB) have emerged as a drug delivery vehicle to overcome the challenges associated with systemic chemotherapy. Here we describe the development of non-immunogenic, functionalized polylactic acid (PLA) MB for use in targeted cancer therapy. Our previous studies have shown that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with two different PEGylation methods, and was best achieved using incorporation of PEG-PLA at 5 wt% and for a LipidPEG at 1 wt%...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28813136/targeting-of-cellular-organelles-by-fluorescent-plasmid-dna-nanoparticles
#10
Diana Costa, Carolina Costa, Margarida Vaz Caldeira, Luisa Maria Cortes, João A Queiroz, Carla Cruz
The development of a suitable delivery system and the targeting of intracellular organelles are both essential for the success of drug and gene therapies. The conception of fluorescent ligands, displaying targeting specificity together with low toxicity, is an emerging and reliable tool to develop innovative delivery systems. Biocompatible BSA or pDNA/ligand nanoparticles were synthesized by a co-precipitation method and were shown to display adequate sizes and morphology for delivery purposes, and positive surface charges...
August 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#11
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28812246/dna-tetrahedron-delivery-enhances-doxorubicin-induced-apoptosis-of-ht-29-colon-cancer-cells
#12
Guiyu Zhang, Zhiyong Zhang, Junen Yang
As a nano-sized drug carrier with the advantage of modifiability and proper biocompatibility, DNA tetrahedron (DNA tetra) delivery is hopeful to enhance the inhibitory efficiency of nontargeted anticancer drugs. In this investigation, doxorubicin (Dox) was assembled to a folic acid-modified DNA tetra via click chemistry to prepare a targeted antitumor agent. Cellular uptake efficiency was measured via fluorescent imaging. Cytotoxicity, inhibition efficiency, and corresponding mechanism on colon cancer cell line HT-29 were evaluated by MTT assay, cell proliferation curve, western blot, and flow cytometry...
August 15, 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28811015/multiple-targeted-graphene-based-nanocarrier-for-intracellular-imaging-of-mrnas
#13
Ying Wang, Zhaohui Li, Misha Liu, Jinjin Xu, Dehong Hu, Yuehe Lin, Jinghong Li
Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1...
August 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28810532/plga-ctab-curcumin-nanoparticles-fabrication-characterization-and-molecular-basis-of-anticancer-activity-in-triple-negative-breast-cancer-cell-lines-mda-mb-231-cells
#14
Ramovatar Meena, Sumit Kumar, Raj Kumar, Usha Singh Gaharwar, Paulraj Rajamani
Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells)...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28810183/computer-modeling-of-drug-delivery-in-the-anterior-human-eye-after-subconjunctival-and-episcleral-implantation
#15
Feng Zhang, Han Chen, Yukan Huang
Recently, subconjunctival and episcleral implants have been proposed in the treatment of anterior eye diseases. In order to improve the delivery efficacy, it is important to understand the transport process of the implanted drugs. A 3D computational model, which includes heat transfer, aqueous humor (AH) flow, as well as diffusive and convective transport of the drug concentration, is developed to study the temporal and spatial evolution of the drug in the anterior segment of a human eye after subconjunctival and episcleral implantation, with a focus on drug delivery to three targets: iris, lens, and trabecular meshwork (TM)...
July 31, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28809432/intranasal-administration-of-brain-targeted-hp-%C3%AE-cd-chitosan-nanoparticles-for-delivery-of-scutellarin-a-compound-with-protective-effect-in-cerebral-ischaemia
#16
Shanshan Liu, Paul C Ho
OBJECTIVES: Scutellarin (SCU) is a traditional Chinese medicine used for the treatment of ischaemic cerebrovascular disease, but its clinic applications have been limited due to its poor water solubility, poor bioavailability and short half-life. In comparison with the conventional oral and intravenous administration, nasal administration may help targeting the drug more directly to brain. Thus, we proposed to employ a novel SCU-loaded HP-β-CD/chitosan nanoparticles (CD/CS-SCU-NPs) to deliver SCU to brain through the nasal route...
August 15, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28809111/tumor-acidic-microenvironment-targeted-drug-delivery-based-on-phlip-modified-mesoporous-organosilica-nanoparticles
#17
Yunlei Zhang, Meng Dang, Ying Tian, Yefei Zhu, Wenfei Liu, Wei Tian, Yunyan Su, Qianqian Ni, Chaoli Xu, Nan Lu, Jun Tao, Yanjun Li, Shuang Zhao, Ying Zhao, Zhenlu Yang, Li Sun, Zhaogang Teng, Guangming Lu
Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we firstly construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment...
August 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28809092/particle-targeting-in-complex-biological-media
#18
REVIEW
Qiong Dai, Nadja Bertleff-Zieschang, Julia A Braunger, Mattias Björnmalm, Christina Cortez-Jugo, Frank Caruso
Over the past few decades, nanoengineered particles have gained increasing interest for applications in the biomedical realm, including diagnosis, imaging, and therapy. When functionalized with targeting ligands, these particles have the potential to interact with specific cells and tissues, and accumulate at desired target sites, reducing side effects and improve overall efficacy in applications such as vaccination and drug delivery. However, when targeted particles enter a complex biological environment, the adsorption of biomolecules and the formation of a surface coating (e...
August 15, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28808971/high-throughput-screening-for-identification-of-novel-innate-immune-activators
#19
Bryan J Gall, Victor R DeFilippis
Modern drug discovery has embraced in vitro platforms that enable investigation of large numbers of compounds within tractable timeframes and for feasible costs. These endeavors have been greatly aided in recent years by advances in molecular and cell-based methods such as gene delivery and editing technology, advanced imaging, robotics, and quantitative analysis. As such, the examination of phenotypic impacts of novel molecules may only be limited by the size of the compound collection. Innate immune signaling processes in mammalian cells are especially amenable to high-throughput screening platforms since the cellular responses elicited by their activation often result in high level transcription that can be harnessed in the form of bioluminescent or fluorescent signal...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808212/recent-advances-in-arsenic-trioxide-encapsulated-nanoparticles-as-drug-delivery-agents-to-solid-cancers
#20
Anam Akhtar, Scarlet Xiaoyan Wang, Lucy Ghali, Celia Bell, Xuesong Wen
Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success...
January 19, 2017: Journal of Biomedical Research
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