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Nanomedicine: Nanotechnology, Biology, and Medicine

Stefano Perni, Polina Prokopovich
The efficient delivery of therapeutic molecules to the cartilage of joints is major obstacle in developing useful therapeutic interventions; hence, a targeted drug delivery system for this tissue is critical. We have overcome the challenge by developing a system that employs electrostatic attraction between the negatively charged constituents of cartilage and a positively charged polymer, Poly-beta amino esters (PBAEs). We have demonstrated cartilage uptake of Dexamethasone (DEX) covalently bound to the PBAE was doubled and retention in tissues prolonged compared to the equivalent dose of the commercial drug formulation...
October 13, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Wei Kevin Zhang, Hong-Wei Gu, Xiao-Jun Li, Yu-Sang Li, He-Bin Tang, Gui-Hua Tian, Hong-Cai Shang
Nano-carriers, especially lipid nanoparticles have been used widely in "a good manner", for instance in the treatment of cancer, by enhancing the targetability and reducing required dose. Here in the contrary, we presented a new possibility: nanoDEN, a nanoparticle-packed "bad guy", which is more effective and efficient in generating liver tumor in mice. We have shown that nanoDEN, same as diethylnitrosamine (DEN), induced overexpression of multiple pivotal factors (including COX-2, β-catenin and PCNA) during oncogenesis...
October 8, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Derrick P McCarthy, Jonathan Woon-Teck Yap, Christopher T Harp, W Kelsey Song, Jeane Chen, Ryan M Pearson, Stephen D Miller, Lonnie D Shea
Tolerogenic nanoparticles (NPs) are rapidly being developed as specific immunotherapies to treat autoimmune disease. However, many NP-based therapies conjugate antigen (Ag) directly to the NP posing safety concerns due to antibody binding or require the co-delivery of immunosuppressants to induce tolerance. Here, we developed Ag encapsulated NPs comprised of poly(lactide-co-glycolide) [PLG(Ag)] and investigated the mechanism of action for Ag-specific tolerance induction in an autoimmune model of T helper type 1/17 dysfunction - relapse-remitting experimental autoimmune encephalomyelitis (R-EAE)...
October 6, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Jye Yng Teo, Willy Chin, Xiyu Ke, Shujun Gao, Shaoqiong Liu, Wei Cheng, James L Hedrick, Yin Yan Yang
Diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable polycarbonate functionalized with GSH-sensitive disulfide bonds and pH-responsive carboxylic acid groups were synthesized using PEG having different molecular weights as macroinitiators through organocatalytic ring-opening polymerization of functional cyclic carbonates. These narrowly-dispersed polymers had predictable molecular weights, which were used to load doxorubicin (DOX) into micelles primarily through ionic interactions. The DOX-loaded micelles exhibited the requisite small particle size (< 100 nm), narrow size distribution and high drug loading capacity...
October 6, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Rinat Meir, Oshra Betzer, Menachem Motiei, Noam Kronfeld, Chaya Brodie, Rachela Popovtzer
Contradictory results in clinical trials are preventing the advancement and implementation of cell-based therapy. To explain such results, there is a need to uncover the mystery regarding the fate of the transplanted cells. To answer this need, we developed a technique for noninvasive in vivo cell tracking, which uses gold nanoparticles as contrast agents for CT imaging. Herein, we investigate the design principles of this technique for intramuscular transplantation of therapeutic cells. Longitudinal studies were performed, displaying the ability to track cells over long periods of time...
October 6, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Yujing Li, Robert J Lee, Xueqin Huang, Yuhuan Li, Bingcong Lv, Tianpeng Wang, Yuhang Qi, Fei Hao, Jiahui Lu, Qingfan Meng, Lirong Teng, Yulin Zhou, Jing Xie, Lesheng Teng
Microfluidic systems can accelerate clinical translation of nanoparticles due to their ability to generate nanoparticles in a well-controlled and reproducible manner. In this study, a single-step process based on microfluidic focusing (MF) was employed to synthesize transferrin-conjugated lipid nanoparticles (Tf-LNPs) and the method was compared with a multi-steps bulk mixing (BM) method. The results indicate that this single-step MF process enables rapid and efficient synthesis of Tf-LNPs, which were named Tf-LNPs-MF...
October 6, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Joana Marques, Juan José Valle-Delgado, Patricia Urbán, Elisabet Baró, Rafel Prohens, Alfredo Mayor, Pau Cisteró, Michael Delves, Robert E Sinden, Christian Grandfils, José L de Paz, José A García-Salcedo, Xavier Fernàndez-Busquets
The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as an heparin surrogate for pRBC targeting...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Laís P Gabriel, Maria Elizabeth M Dos Santos, André L Jardini, Gilmara N T Bastos, Carmen G B T Dias, Thomas J Webster, Rubens Maciel Filho
In this work, thermoset polyurethane composites were prepared by the addition of hydroxyapatite nanoparticles using the reactants polyol polyether and an aliphatic diisocyanate. The polyol employed in this study was extracted from the Euterpe oleracea Mart. seeds from the Amazon Region of Brazil. The influence of hydroxyapatite nanoparticles on the structure and morphology of the composites was studied using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), the structure was evaluated by Fourier transform infrared spectroscopy (FT-IR), thermal properties were analyzed by thermogravimetry analysis (TGA), and biological properties were studied by in vitro and in vivo studies...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Simona Ghiani, Martina Capozza, Claudia Cabella, Alessandra Coppo, Luigi Miragoli, Chiara Brioschi, Roberta Bonafè, Alessandro Maiocchi
The current study was performed to evaluate the in vivo efficiency of a new nano-sized contrast agent called paramagnetic Solid Lipid Nanoparticles, pSLNs, having promising relaxivity properties for Magnetic Resonance Imaging application. Good stability and stealth properties towards macrophage uptake have been demonstrated. An in vivo MRI study resulted in an improved signal enhancement in the tumor tissue particularly when folate as targeting ligand was used to decorate the nanoparticles surface. Afterwards, the biodistribution of pSLNs in several organs was investigated...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Yanbing Zu, Min-Han Tan, Chee Ren Ee, Jackie Y Ying
A number of human leukocyte antigen (HLA) gene alleles have been found to be genetic risk markers for immunologically mediated drug hypersensitivity. Clinical adoption of HLA pharmacogenomics requires facile and accurate allele screening assays. As HLA genes are highly polymorphic, currently available methods are usually labor-intensive and liable to generate false positives. Herein we report a general strategy for screening HLA alleles with nanoparticle probes. Specific HLA alleles can be identified by gauging three to five sequence variants...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Andrew T Lucas, Taylor F White, Allison M Deal, Leah B Herity, Gina Song, Charlene M Santos, William C Zamboni
The mononuclear phagocyte system (MPS) has previously been shown to significantly affect the clearance, tumor delivery, and efficacy of nanoparticles (NPs). This study profiled MPS cell infiltration in murine preclinical tumor models and evaluated how these differences may affect tumor disposition of PEGylated liposomal doxorubicin (PLD) in models sensitive and resistant to PLD. Significant differences in MPS presence existed between tumor types (e.g. ovarian versus endometrial), cell lines within the same tumor type, and location of tumor implantation (i...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Nadya Velikova, Nuria Mas, Laura Miguel-Romero, Lorena Polo Aguado, Ellen Stolte, Edoardo Zaccaria, Rui Cao, Nico Taverne, José Ramón Murguía, Ramon Martinez-Manez, Alberto Marina, Jerry Wells
Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into ε-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr-) permeability barrier for the HKAIs. The observed bactericidal activity against Gr- bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Pramod Jagtap, Venkataraman Sritharan, Shalini Gupta
Bloodstream bacterial infections are a serious threat to global public health and economy. The recent figures released by National Center for Health Statistics indicate that more than a million Americans get affected by it each year and the sepsis mortality alone is about 28%-50% (Hall et al., 2011). Hall et al. (2011) (1) Robust and affordable point-of-care medical technologies are, therefore, urgently needed for rapid decision-making to initiate appropriate line of treatment. Current techniques based on blood culture and serology do not have quick turnaround times or adequate sensitivities for early intervention...
October 1, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Clara L Essmann, Muna Elmi, Mike Shaw, Giridhar M Anand, Vijay M Pawar, Mandayam A Srinivasan
Atomic force microscopy (AFM) is a powerful method for topographic imaging of surfaces with nanometer resolution. AFM offers significant advantages over scanning electron microscopy (SEM) including the acquisition of quantitative 3D-images and biomechanical information. More importantly, for in-vivo biological imaging, AFM does not require sample dehydration/labeling. We show for the first time high-resolution topographical images of the cuticle of the model organism C. elegans under physiological conditions using AFM...
October 1, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Hannah Pischon, Moritz Radbruch, Anja Ostrowski, Pierre Volz, Christian Gerecke, Michael Unbehauen, Stefan Hönzke, Sarah Hedtrich, Joachim W Fluhr, Rainer Haag, Burkhard Kleuser, Ulrike Alexiev, Achim D Gruber, Lars Mundhenk
Inflammatory disorders of the skin pose particular therapeutic challenges due to complex structural and functional alterations of the skin barrier. Penetration of several anti-inflammatory drugs is particularly problematic in psoriasis, a common dermatitis condition with epidermal hyperplasia and hyperkeratosis. Here, we tested in vivo dermal penetration and biological effects of dendritic core-multishell-nanocarriers (CMS) in a murine skin model of psoriasis and compared it to healthy skin. In both groups, CMS exclusively localized to the stratum corneum of the epidermis with only very sporadic uptake by Langerhans cells...
October 1, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Peiyan Yuan, Xin Ding, Nengyue Gao, Hai Zhu, Yan Yang Yi, Qing-Hua Xu
Au@Ag nanoparticles (NPs) were recently found to display giant two-photon photoluminescence (2PPL) enhancement, with an enhancement factor up to 815 fold upon aggregate formation. Based on this finding, two-photon imaging of bacteria by Au@Ag NPs under near-infrared (NIR) femtosecond laser pulses was demonstrated in this study, as positively charged Au@Ag NPs can form aggregates on the negatively charged bacterial surface, yielding strong 2PPL emission. The aggregation-enhanced 2PPL of Au@Ag NPs stemmed from higher two-photon excitation efficiency, implying strong two-photon photothermal effects...
October 1, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Ning Huang, Si Cheng, Xiang Zhang, Qi Tian, Jiangli Pi, Jun Tang, Qin Huang, Feng Wang, Jin Chen, Zongyi Xie, Zhongye Xu, Weifu Chen, Huzhi Zheng, Yuan Cheng
Delivery of imaging agents to brain glioma is challenging because the blood-brain barrier(BBB) functions as a physiological checkpoint guarding the central nervous system from circulating large molecules. Moreover, the ability of existing probes to target glioma has been insufficient and needs to be improved. In present study, PEG-based long circulation, CdSe/ZnS quantum dots(QDs)-based nanoscale and fluorescence, asparagines-glycine-arginine peptides(NGR)-based specific CD13 recognition were integrated to design and synthesize a novel nanoprobe by conjugating biotinylated NGR peptides to avidin-PEG-coated QDs...
September 25, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Li Wang, Timothy Z Chang, Yuan He, Jong R Kim, Shelly Wang, Teena Mohan, Zachary Berman, S Mark Tompkins, Ralph A Tripp, Richard W Compans, Julie A Champion, Bao-Zhong Wang
Recurring influenza viruses pose an annual threat to public health. A time-saving, cost-effective and egg-independent influenza vaccine approach is important particularly when responding to an emerging pandemic. We fabricated coated, two-layer protein nanoclusters from recombinant trimeric hemagglutinin from an avian-origin H7N9 influenza A virus as an approach for vaccine development in response to an emerging pandemic. Assessment of the virus-specific immune responses and protective efficacy in mice immunized with the nanoclusters demonstrated that the vaccine candidates were highly immunogenic, able to induce protective immunity and long-lasting humoral antibody responses to this virus without the use of adjuvants...
September 10, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Zebin Ma, Huan Qin, Hongjiang Chen, Hailong Yang, Jiankun Xu, Sihua Yang, Jun Hu, Da Xing
Specific detection of various tumor types remains crucial for designing effective treatment strategies. We demonstrate photoacoustic imaging (PAI) using high-affinity and high-specificity peptide-based probes for accurate and specific diagnosis of osteosarcoma. Herein, two new tumor-specific oligopeptides, termed PT6 and PT7, were identified using phage display-based screening on an osteosarcoma cell line (UMR-106). The identified oligopeptides were able to detect clinical osteosarcoma samples on tissue microarrays...
September 10, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Rebeca Penalva, Carlos J González-Navarro, Carlos Gamazo, Irene Esparza, Juan M Irache
Zein nanoparticles were evaluated as nanocarriers to promote the oral bioavailability of quercetin and, thus, improve its anti-inflammatory effect on a mouse model of induced endotoxemia. For this purpose, the flavonoid and 2-hydroxypropyl-β-cyclodextrin were encapsulated in zein nanoparticles. The resulting nanoparticles displayed a mean size of about 300nm and the payload was calculated to be close to 70μg/mg nanoparticle. The release of quercetin from zein nanoparticles followed a zero-order kinetic. After oral administration, nanoparticles provided high and sustained levels of quercetin in plasma and the relative oral bioavailability was calculated to be approx...
September 8, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
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