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Chen-Xu Ni, Yang Qi, Jin Zhang, Ying Liu, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Qiu-Ye Wu, Yan Wang, Jun-Ping Zhang
The eradication of cancer stem cells (CSCs) is significant for cancer therapy and prevention. In this study, we evaluated WM130, a novel derivative of matrine, for its effect on CSCs using human hepatocellular carcinoma (HCC) cell lines, their sphere cells, and sorted EpCAM+ cells. We revealed that WM130 could not only inhibit proliferation and colony formation of HCC cells, but also suppress the expression of some stemness-related genes and up-regulate some mature hepatocyte marker genes, indicating a promotion of differentiation from CSCs to hepatocytes...
October 22, 2016: Oncotarget
Subhajit Ghosh, Saswat Mohapatra, Anisha Thomas, Debmalya Bhunia, Abhijit Saha, Gaurav Das, Batakrishna Jana, Surajit Ghosh
An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics, competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find out such a unique nanocarrier and engineer all the above-mentioned features into it. In this manuscript, we have shown for the first time that Apoferritin (Apf) can carry and deliver high dose of doxorubicin (Dox), docetaxel (Doc) and combination of both Dox and Doc specifically into the cancer cell and enhances killing compared to free drug without any functionalization or property modulation...
October 26, 2016: ACS Applied Materials & Interfaces
Scott Edmonds, Alessia Volpe, Hilary Shmeeda, Ana C Parente-Pereira, Riya Radia, Julia Baguña-Torres, Istvan Szanda, Gregory W Severin, Lefteris Livieratos, Philip J Blower, John Maher, Gilbert O Fruhwirth, Alberto Gabizon, Rafael T M de Rosales
The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as liposomal drugs with PET radionuclides will have a wide impact in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling method that exploits the metal-chelating properties of certain drugs (e.g., bisphosphonates such as alendronate and anthracyclines such as doxorubicin) and widely used ionophores to achieve excellent radiolabeling yields, purities, and stabilities with (89)Zr, (52)Mn, and (64)Cu, and without the requirement of modification of the nanomedicine components...
October 26, 2016: ACS Nano
Yoonjee C Park, Chentian Zhang, Sudong Kim, Graciela Mohamedi, Carl Beigie, Jon O Nagy, R Glynn Holt, Robin O Cleveland, Noo Li Jeon, Joyce Y Wong
Microbubbles have been used in ultrasound-assisted drug delivery to help target solid tumors via blood vessels in vivo; however, studies to understand the phenomena at the cellular level and to optimize parameters for ultrasound or microbubbles in vivo are challenging and expensive to perform. Here, we utilize microfluidic microvessels-on-a-chip that enable visualization of microbubble/ultrasound-dependent drug delivery to microvasculature. When exposed to pulsed ultrasound, microbubbles perfused through microvessels-on-a-chip were observed to stably oscillate...
October 26, 2016: ACS Applied Materials & Interfaces
Marta Denel-Bobrowska, Małgorzata Łukawska, Aneta Rogalska, Ewa Forma, Magdalena Bryś, Irena Oszczapowicz, Agnieszka Marczak
Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are novel anthracycline derivatives with a modified daunosamine moiety. In the present study, we evaluated the cytotoxicities, genotoxicities and abilities of O-DOX and O-DAU to induce apoptosis in cancer cell lines (SKOV-3; A549; HepG2), and compared the results with their parent drugs. We assessed antiproliferative activity by MTT assay. We evaluated apoptosis-inducing ability by double-staining with fluorescent probes (Hoechst 33258/propidium iodide), and by determining expression levels of genes involved in programmed cell death by reverse transcription-polymerase chain reaction...
October 22, 2016: Toxicology and Applied Pharmacology
Meng Wang, Ying Li, Mingyi HuangFu, Yi Xiao, Tianyuan Zhang, Min Han, Donghang Xu, Fangyuan Li, Daishun Ling, Yi Jin, Jianqing Gao
AIM: To design pluronic F68 (PF68)-conjugated polyamidoamine (PAMAM) dendrimer conjugates for doxorubicin (DOX) delivery for overcoming multidrug resistance, and clarify the reversal mechanism. MATERIALS & METHODS: A series of PAMAM-PF68 conjugates were designed. The antitumor activity of the DOX-loaded conjugates was evaluated against MCF-7/ADR cells, tumor spheroids and tumors. Several bioinformatics were detected to characterize the reversal mechanism. RESULTS: Increased antitumor activity of the DOX-loaded conjugates was achieved in vitro and in vivo...
October 26, 2016: Nanomedicine
Gregory F Guzauskas, Kathleen F Villa, Geertrui F Vanhove, Vicki L Fisher, David L Veenstra
PURPOSE: To estimate the risk-benefit trade-off of a pediatric-inspired regimen versus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) for first-line treatment of adolescents/young adult (AYA; ages 16-39 years) patients with Philadelphia-negative acute lymphoblastic leukemia. METHODS: Patient outcomes were simulated using a 6-state Markov model, including complete response (CR), no CR, first relapse, second CR, second relapse, and death...
October 25, 2016: Journal of Adolescent and Young Adult Oncology
Mariam S Aboian, Jay F Yu, Ayushi Gautam, Chia-Hung Sze, Jeffrey K Yang, Jonathan Chan, Prasheel V Lillaney, Caroline D Jordan, Hee-Jeung Oh, David M Wilson, Anand S Patel, Mark W Wilson, Steven W Hetts
To report a novel method using immobilized DNA within mesh to sequester drugs that have intrinsic DNA binding characteristics directly from flowing blood. DNA binding experiments were carried out in vitro with doxorubicin in saline (PBS solution), porcine serum, and porcine blood. Genomic DNA was used to identify the concentration of DNA that shows optimum binding clearance of doxorubicin from solution. Doxorubicin binding kinetics by DNA enclosed within porous mesh bags was evaluated. Flow model simulating blood flow in the inferior vena cava was used to determine in vitro binding kinetics between doxorubicin and DNA...
December 2016: Biomedical Microdevices
Hannah H Lee, Brenda F Leake, Richard B Kim, Richard H Ho
The organic anion-transporting polypeptides represent an important family of drug uptake transporters that mediate the cellular uptake of a broad range of substrates including numerous drugs. Doxorubicin is a highly efficacious and well-established anthracycline chemotherapeutic agent commonly used in the treatment of a wide range of cancers. While doxorubicin is a known substrate for efflux transporters such as P-glycoprotein (P-gp; MDR1, ABCB1), significantly less is known regarding its interactions with drug uptake transporters...
October 24, 2016: Molecular Pharmacology
Yu Zhang, Yifei Lu, Feng Wang, Sai An, Yujie Zhang, Tao Sun, Jianhua Zhu, Chen Jiang
Inflammation has been reported as one significant hallmark of breast cancer in relation to tumor development, metastasis, and invasion. The bradykinin receptor 1 (B1R) is highly expressed on inflammatory breast tumor cells thus providing a promising targeting site for tumor recognition and sufficient receptor mediated endocytosis. In this study, the authors evaluate the targeting efficiency of l-form and d-form [des-Arg(10) ]kallidin both in vitro and in vivo. To further improve the drug delivery efficiency, the authors establish a dandelion like nanoparticle by combining the polymeric drug conjugates and aptamer complex together...
October 24, 2016: Small
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
Aldo Isaac Martínez-Banderas, Antonio Aires, Francisco J Teran, Jose Efrain Perez, Jael F Cadenas, Nouf Alsharif, Timothy Ravasi, Aitziber L Cortajarena, Jürgen Kosel
Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX...
October 24, 2016: Scientific Reports
Jun-Qing Situ, Xiao-Juan Wang, Xiu-Liang Zhu, Xiao-Ling Xu, Xu-Qi Kang, Jing-Bo Hu, Chen-Ying Lu, Xiao-Ying Ying, Ri-Sheng Yu, Jian You, Yong-Zhong Du
Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL(-1) and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI...
October 24, 2016: Scientific Reports
Hyung-Youl Park, Sreekantha Reddy Dugasani, Dong-Ho Kang, Gwangwe Yoo, Jinok Kim, Bramaramba Gnapareddy, Jaeho Jeon, Minwoo Kim, Young Jae Song, Sungjoo Lee, Jonggon Heo, Young Jin Jeon, Sung Ha Park, Jin-Hong Park
Here, we report a high performance biosensor based on (i) a Cu(2+)-DNA/MoS2 hybrid structure and (ii) a field effect transistor, which we refer to as a bio-FET, presenting a high sensitivity of 1.7 × 10(3) A/A. This high sensitivity was achieved by using a DNA nanostructure with copper ions (Cu(2+)) that induced a positive polarity in the DNA (receptor). This strategy improved the detecting ability for doxorubicin-like molecules (target) that have a negative polarity. Very short distance between the biomolecules and the sensor surface was obtained without using a dielectric layer, contributing to the high sensitivity...
October 24, 2016: Scientific Reports
Sebastian Hörner, Sascha Knauer, Christina Uth, Marina Jöst, Volker Schmidts, Holm Frauendorf, Christina Marie Thiele, Olga Avrutina, Harald Kolmar
We report a comprehensive study on novel, highly efficient, and biodegradable hybrid molecular transporters. To this end, we designed a series of cell-penetrating, cube-octameric silsesquioxanes (COSS), and investigated cellular uptake by confocal microscopy and flow cytometry. A COSS with dense spatial arrangement of guanidinium groups displayed fast uptake kinetics and cell permeation at nanomolar concentrations in living HeLa cells. Efficient uptake was also observed in bacteria, yeasts, and archaea. The COSS-based carrier was significantly more potent than cell-penetrating peptides (CPPs) and displayed low toxicity...
October 24, 2016: Angewandte Chemie
Sen Lin, Tong Li, Peiling Xie, Qing Li, Bailiang Wang, Lei Wang, Lingli Li, Yuqin Wang, Hao Chen, Kaihui Nan
Targeted delivery of cytotoxic drugs to tumour tissue has great importance for successful chemotherapy. Legumain is an asparaginyl endopeptidase that is highly up-regulated in a number of solid tumours. The aim of this work was to prepare a novel hyaluronic acid (HA) based legumain sensitive nanogel for the delivery of doxorubicin with a high targeting efficiency both in vitro and in vivo. The legumain sensitive property is achieved by the conjugation of doxorubicin with HA via a legumain substrate peptide bridge...
October 24, 2016: Nanoscale
Lei Mei, Guizhi Zhu, Liping Qiu, Cuichen Wu, Huapei Chen, Hao Liang, Sena Cansiz, Yifan Lv, Xiaobing Zhang, Weihong Tan
Cancer chemotherapy has been impeded by side effects and multidrug resistance (MDR) partially caused by drug efflux from cancer cells, which call for targeted drug delivery systems additionally able to circumvent MDR. Here we report multifunctional DNA nanoflowers (NFs) for targeted drug delivery to both chemosensitive and MDR cancer cells and circumvent MDR in both leukemia and breast cancer cell models. NFs are self-assembled via liquid crystallization of DNA generated by Rolling Circle Replication, during which NFs are incorporated with aptamers for specific cancer cell recognition, fluorophores for bioimaging, and Doxorubicin (Dox)-binding DNA for drug delivery...
November 2015: Nano Research
Thu Thao Nguyen Thi, Tuong Vi Tran, Ngoc Quyen Tran, Cuu Khoa Nguyen, Dai Hai Nguyen
Porous nanosilica (PNS) has been attracting a great attention in fabrication carriers for drug delivery system (DDS). However, unmodified PNS-based carriers exhibited the initial burst release of loaded bioactive molecules, which may limit their potential clinical application. In this study, the surface of PNS was conjugated with adamantylamine (A) via disulfide bonds (PNS-SS-A) which was functionalized with cyclodextrin-heparin-polyethylene glycol (CD-HPEG) for redox triggered doxorubicin (DOX) delivery. The modified PNS was successfully formed with spherical shape and diameter around 50nm determined by transmission electron microscopy (TEM)...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Anna Mielańczyk, Justyna Odrobińska, Sebastian Grządka, Łukasz Mielańczyk, Dorota Neugebauer
The β-glucoside-based heterofunctional initiator was used in the synthesis of well-defined eight-armed miktopolymers by sequential ring opening polymerization (ROP) of ε-caprolactone (CL) and atom transfer radical (co)polymerization (ATRP) of methyl methacrylate (MMA) and/or tert-butyl methacrylate (tBMA). Consequently, methacrylic acid (MAA) repeating units were introduced via selective cleavage of pendant tert-butyl protecting groups. Both the amphiphilic copolymers and miktoarm copolymers were self-assembled at 37°C and pH 7...
October 19, 2016: International Journal of Pharmaceutics
Yinping Huang, Kaili Mao, Baolin Zhang, Yingzheng Zhao
Monodispersed SPIONs (superparamagnetic iron oxide nanoparticles) co-coated with PEG and PEI polymers were prepared by an improved polyol method. To accomplish cancer-specific targeting properties, FA (folic acid) was then modified on the SPIONs via EDC/NHS method (FA-SPIONs). Doxorubicin (DOX) as an example anticancer drug was loaded within FA-SPIONs (DOX@FA-SPIONs), the DOX release rate of DOX@FA-SPIONs was much high in low pH PBS. The SPIONs, FA-SPIONs and DOX@FA-SPIONs with mean hydrodynamic diameters of 23, 40 and 67nm, respectively, performed excellent colloidal stability in PBS...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
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