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Marco Giardiello, Neill J Liptrott, Tom O McDonald, Darren Moss, Marco Siccardi, Phil Martin, Darren Smith, Rohan Gurjar, Steve P Rannard, Andrew Owen
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral...
October 21, 2016: Nature Communications
Louis T Curtis, Hermann B Frieboes
Although extensive research effort and resources have been dedicated to the development of nanotherapeutics to treat cancer, few formulations have reached clinical application. A major reason is that the large number of parameters available to tune nanotherapy characteristics coupled with the variability in tumor tissue precludes evaluation of complex interactions through experimentation alone. In order to optimize the nanotechnology design and gain further insight into these phenomena, mathematical modeling and computational simulation have been applied to complement empirical work...
2016: Advances in Experimental Medicine and Biology
Dean Ho, Ali Zarrinpar, Edward Kai-Hua Chow
The field of nanomedicine has already seen substantial progress in the clinic, with multiple formulations being evaluated through clinical studies. From poly(lactic-co-glycolic acid) and cyclodextrin-based drug-delivery platforms to metallic nanoparticles for photothermal treatment and imaging, nanotechnology has enabled versatile strategies to treat and to diagnose a wide range of disorders. However, as the field as a whole pushes forward, barriers that have always challenged conventional drug development have already started to impact nanomedicine translation...
September 28, 2016: ACS Nano
Huimin Yan, Xin Duan, Hua Pan, Nilsson Holguin, Muhammad Farooq Rai, Antonina Akk, Luke E Springer, Samuel A Wickline, Linda J Sandell, Christine T N Pham
Osteoarthritis (OA) is a major cause of disability and morbidity in the aging population. Joint injury leads to cartilage damage, a known determinant for subsequent development of posttraumatic OA, which accounts for 12% of all OA. Understanding the early molecular and cellular responses postinjury may provide targets for therapeutic interventions that limit articular degeneration. Using a murine model of controlled knee joint impact injury that allows the examination of cartilage responses to injury at specific time points, we show that intraarticular delivery of a peptidic nanoparticle complexed to NF-κB siRNA significantly reduces early chondrocyte apoptosis and reactive synovitis...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Marwan Moussa, S Nahum Goldberg, Gaurav Kumar, Tatyana Levchenko, Vladimir Torchilin, Muneeb Ahmed
PURPOSE: The aim of this study was to evaluate the effect of different radio-frequency ablation (RFA) thermal doses on coagulation and heat shock protein (HSP) response with and without adjuvant nanotherapies. MATERIALS AND METHODS: First, Fischer rats were assigned to nine different thermal doses of hepatic RFA (50-90 °C, 2-20 min, three per group) or no treatment (n = 3). Next, five of these RF thermal doses were combined with liposomal-doxorubicin (Lipo-Dox, 1 mg intravenously) in R3230 breast tumours, or no tumour treatment (five per group)...
December 2016: International Journal of Hyperthermia
Saqlain A Shah, M U Aslam Khan, M Arshad, S U Awan, M U Hashmi, N Ahmad
Multifunctional magnetic nanosystems have attracted an enormous attention of researchers for their potential applications in cancer diagnostics and therapy. The localized nanotherapies triggered by the external stimuli, like magnetic fields and visible light, are significant in clinical applications. We report a liposomal system that aims to treat cancer by magnetic hyperthermia, photodynamic therapy and chemotherapy simultaneously. The liposomes enclose clinically used photosensitizer m-THPC (Foscan) and anti-cancer drug doxorubicin, in its hydrophobic lipid bilayers, and contains magnetite nanoparticles in hydrophilic core...
August 31, 2016: Colloids and Surfaces. B, Biointerfaces
(no author information available yet)
No abstract text is available yet for this article.
September 1, 2016: Cancer Research
Suresh Gadde, Katey J Rayner
Cardiovascular disease (CVD) accounts for almost half of all deaths worldwide and has now surpassed infectious disease as the leading cause of death and disability in developing countries. At present, therapies such as low-density lipoprotein-lowering statins and antihypertensive drugs have begun to bend the morality curve for coronary artery disease (CAD); yet, as we come to appreciate the more complex pathophysiological processes in the vessel wall, there is an opportunity to fine-tune therapies to more directly target mechanisms that drive CAD...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Qixiong Zhang, Hui Tao, Yongyao Lin, Ying Hu, Huijie An, Dinglin Zhang, Shibin Feng, Houyuan Hu, Ruibing Wang, Xiaohui Li, Jianxiang Zhang
Oxidative stress, resulting from excessive generation of reactive oxygen species (ROS), plays a pivotal role in the initiation and progression of inflammatory bowel disease (IBD). To develop an efficacious and safe nanotherapy against IBD, we designed and developed a superoxide dismutase/catalase mimetic nanomedicine comprising a hydrogen peroxide-eliminating nanomatrix and a free radical scavenger Tempol (Tpl). To this end, an oxidation-responsive β-cyclodextrin material (OxbCD) was synthesized, and a Tpl-loaded OxbCD nanoparticle (Tpl/OxbCD NP) was produced...
October 2016: Biomaterials
Shibin Feng, Ying Hu, Song Peng, Songling Han, Hui Tao, Qixiong Zhang, Xiaoqiu Xu, Jianxiang Zhang, Houyuan Hu
Coronary arterial disease (CAD) remains the leading cause of death globally. Percutaneous coronary interventions are frequently used nonsurgical techniques for treating CAD, which may unfortunately lead to arterial restenosis. Currently, there are no effective drugs that can thoroughly prevent restenosis. We hypothesize inflammation-triggerable nanomedicines may function as effective therapeutics for targeted therapy of restenosis, by preferentially releasing their payload at the diseased site. To demonstrate our hypothesis and develop targeted nanotherapies for restenosis, this study was designed to examine effectiveness of nanomedicines responsive to the inflammatory microenvironment with mild acidity and high reactive oxygen species (ROS)...
October 2016: Biomaterials
Monica Neagu, Zoi Piperigkou, Konstantina Karamanou, Ayse Basak Engin, Anca Oana Docea, Carolina Constantin, Carolina Negrei, Dragana Nikitovic, Aristidis Tsatsakis
With the expansion of the nanomedicine field, the knowledge focusing on the behavior of nanoparticles in the biological milieu has rapidly escalated. Upon introduction to a complex biological system, nanomaterials dynamically interact with all the encountered biomolecules and form the protein "bio-corona." The decoration with these surface biomolecules endows nanoparticles with new properties. The present review will address updates of the protein bio-corona characteristics as influenced by nanoparticle's physicochemical properties and by the particularities of the encountered biological milieu...
July 20, 2016: Archives of Toxicology
Alexander J Donovan, Joseph Kalkowski, Magdalena Szymusiak, Canhui Wang, Stephanie A Smith, Robert F Klie, James H Morrissey, Ying Liu
Granular platelet-sized polyphosphate nanoparticles (polyP NPs) were encapsulated in sterically stabilized liposomes, forming a potential, targeted procoagulant nanotherapy resembling human platelet dense granules in both structure and functionality. Dynamic light scattering (DLS) measurements reveal that artificial dense granules (ADGs) are colloidally stable and that the granular polyP NPs are encapsulated at high efficiencies. High-resolution scanning transmission electron microscopy (HR-STEM) indicates that the ADGs are monodisperse particles with a 150 nm diameter dense core consisting of P, Ca, and O surrounded by a corrugated 25 nm thick shell containing P, C, and O...
August 8, 2016: Biomacromolecules
Yanlan Liu, Viswanath Gunda, Xi Zhu, Xiaoding Xu, Jun Wu, Diana Askhatova, Omid C Farokhzad, Sareh Parangi, Jinjun Shi
Anaplastic thyroid cancer (ATC), one of the most aggressive solid tumors, is characterized by rapid tumor growth and severe metastasis to other organs. Owing to the lack of effective treatment options, ATC has a mortality rate of ∼100% and median survival of less than 5 months. RNAi nanotechnology represents a promising strategy for cancer therapy through nanoparticle (NP) -mediated delivery of RNAi agents (e.g., siRNA) to solid tumors for specific silencing of target genes driving growth and/or metastasis...
July 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
Carlos Pérez-Medina, Dalya Abdel-Atti, Jun Tang, Yiming Zhao, Zahi A Fayad, Jason S Lewis, Willem J M Mulder, Thomas Reiner
The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co-injecting Doxil and a Zirconium-89 nanoreporter ((89)Zr-NRep) allows precise doxorubicin (DOX) quantification...
2016: Nature Communications
João Conde, Nuria Oliva, Natalie Artzi
The promise of (nano)biomaterials for the treatment of cancer can only be realized following a comprehensive scrutiny of the tumor microenvironment. The generic use of 'inert' vehicles that deliver a specific cargo to treat a range of cancer types and disease states obeys the 'one material fits all' rule. However, this approach leads to suboptimal and unpredictable clinical outcomes. The key factors constructing the tumor milieu should guide the design of disease-responsive materials. Given the growing availability of nanomaterials for cancer therapy, a material that responds to each patient's needs and, hence, reacts in a graded manner based on disease cues, would pave the way to precision materials for cancer therapy...
August 2016: Trends in Biotechnology
Yin Dou, Jiawei Guo, Yue Chen, Songling Han, Xiaoqiu Xu, Qing Shi, Yi Jia, Ya Liu, Youcai Deng, Ruibing Wang, Xiaohui Li, Jianxiang Zhang
Increasing evidence has demonstrated special advantages of the nanomedicinal approach for the management of cardiovascular disease. We hypothesize that sustained delivery of rapamycin (RAP) may provide more desirable therapeutic effects than traditional oral administration by selectively inhibiting mammalian target of rapamycin complex 1 (mTORC1) signaling. To evidence this assumption and develop an effective, safe, and translational nanotherapy for atherosclerosis, this study was designed to examine antiatherosclerotic efficacy of a RAP nanotherapy based on an acetalated β-cyclodextrin (Ac-bCD) material in apolipoprotein E-deficient (ApoE(-/-)) mice...
August 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Paola Sánchez-Moreno, Juan Luis Ortega-Vinuesa, José Manuel Peula-García, Juan Antonio Marchal, Houria Boulaiz
Despite all the advances achieved in the field of tumor-biology research, in most cases conventional therapies including chemotherapy are still the leading choices. The main disadvantage of these treatments, in addition to the low solubility of many antitumor drugs, is their lack of specificity, which leads to the occurrence of severe side effects due to nonspecific drug uptake by healthy cells. Progress in nanotechnology and its application in medicine have provided new opportunities and different smart systems...
May 27, 2016: Current Drug Targets
Yanhua Zhang, Janelle Buttry Walker, Zeljka Minic, Fangchao Liu, Harry Goshgarian, Guangzhao Mao
Drug delivery to the central nervous system (CNS) is challenging due to the inability of many drugs to cross the blood-brain barrier (BBB). Here, we show that wheat germ agglutinin horse radish peroxidase (WGA-HRP) chemically conjugated to gold nanoparticles (AuNPs) can be transported to the spinal cord and brainstem following intramuscular injection into the diaphragm of rats. We synthesized and determined the size and chemical composition of a three-part nanoconjugate consisting of WGA-HRP, AuNPs, and drugs for the treatment of diaphragm paralysis associated with high cervical spinal cord injury (SCI)...
2016: Scientific Reports
Monica Madalina Tucureanu, Elena Butoi, Ana-Maria Gan, Daniela Stan, Cristina Ana Constantinescu, Manuela Calin, Maya Simionescu, Ileana Manduteanu
In atherosclerotic plaques, macrophages (MAC) and smooth muscle cells (SMC) frequently reside in close proximity and resistin (Rs) and fractalkine (Fk) are present at increased levels, resistin being associated with CD68 macrophages and fractalkine predominantly associated with intimal SMC; however, their role in this location is not clear, yet. The objective of this study was to determine whether the cross-talk between MAC-SMC induces changes in MAC cytokine phenotype and if Fk and Rs have a role in the process...
July 2016: Cytokine
Ravikumar Aalinkeel, Bindukumar Nair, Chih-Kuang Chen, Supriya D Mahajan, Jessica L Reynolds, Hanguang Zhang, Haotian Sun, Donald E Sykes, Kailash C Chadha, Steven G Turowski, Katelyn D Bothwell, Mukund Seshadri, Chong Cheng, Stanley A Schwartz
Interleukin-8 (IL-8) is a pro-angiogenic cytokine associated with aggressive prostate cancer (CaP). We detected high levels of IL-8 in sera from patients with CaP compared with healthy controls and patients with benign prostatic hypertrophy. This study examines the role of IL-8 in the pathogenesis of metastatic prostate cancer. We developed a biocompatible, cationic polylactide (CPLA) nanocarrier to complex with and efficiently deliver IL-8 small interfering RNA (siRNA) to CaP cells in vitro and in vivo. CPLA IL-8 siRNA nanocomplexes (nanoplexes) protect siRNA from rapid degradation, are non-toxic, have a prolonged lifetime in circulation, and their net positive charge facilitates penetration of cell membranes and subsequent intracellular trafficking...
August 2016: Immunology
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