Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction:An In Vitro and In Vivo Study

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above-mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI-selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages. The system based on pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor-dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self-renewal promoting compounds, CHIR99021 and SB203580, induces a 4-fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2-like macrophages targeting by lin-TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short-term safety of the developed system in vivo. Overall, the study results in the development of a peptide-guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart

Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction:An In Vitro and In Vivo Study

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above-mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI-selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages. The system based on pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor-dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self-renewal promoting compounds, CHIR99021 and SB203580, induces a 4-fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2-like macrophages targeting by lin-TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short-term safety of the developed system in vivo. Overall, the study results in the development of a peptide-guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart

Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction:An In Vitro and In Vivo Study

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above-mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI-selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages. The system based on pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor-dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self-renewal promoting compounds, CHIR99021 and SB203580, induces a 4-fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2-like macrophages targeting by lin-TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short-term safety of the developed system in vivo. Overall, the study results in the development of a peptide-guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart

Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction:An In Vitro and In Vivo Study

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above-mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI-selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages. The system based on pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor-dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self-renewal promoting compounds, CHIR99021 and SB203580, induces a 4-fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2-like macrophages targeting by lin-TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short-term safety of the developed system in vivo. Overall, the study results in the development of a peptide-guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart

Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction:An In Vitro and In Vivo Study

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above-mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI-selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages. The system based on pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor-dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self-renewal promoting compounds, CHIR99021 and SB203580, induces a 4-fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2-like macrophages targeting by lin-TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short-term safety of the developed system in vivo. Overall, the study results in the development of a peptide-guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart

Therapeutic Antibody Against Phosphorylcholine Preserves Coronary Function and Attenuates Vascular 18F-FDG Uptake in Atherosclerotic Mice

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of 18F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.</p

Three-dimensional geometry-based radio channel model:parametrization and validation at 10 GHz

Abstract This dissertation presents complete parameterizations for a three-dimensional (3-D) geometry-based stochastic radio channel model (GSCM) at 10 GHz based on measurement campaigns. The thesis is divided into the following main parts: radio channel measurements, the characterization of model parameters, and model validation. Experimental multiple-input multiple-output (MIMO) channel measurements carried out in two-story lobby and urban small cell scenarios are first described. The measurements were performed with a vector network analyzer and dual polarized virtual antenna arrays with a bandwidth over 500 MHz. The measurement data was post-processed using the ESPRIT algorithm and the post-processed data was verified using a semi-deterministic map-based model. The results showed a good match between estimated and modeled multipath components (MPCs). In addition, single-input single-output outdoor-to-indoor measurements were executed through a standard multi-pane glass window and concrete wall. A statistical analysis was carried out for defining full 3-D characterization of the propagation channel in both line-of-sight (LOS) and non-line-of-sight (NLOS) propagation conditions. The delay and angular dispersions of MPCs are smaller in comparison to lower frequency bands due to the higher attenuation of the delayed MPCs. Moreover, specular reflection is observed to be the more dominant propagation mechanism in comparison to diffuse scattering, leading to smaller cluster angle spreads in comparison to lower frequency bands. The penetration loss caused by a standard multi-pane glass window is on the same level as in the lower frequency bands, whereas the loss caused by the concrete wall is a few dBs higher than at lower frequency bands. Finally, the GSCM with determined parameters is validated. A MIMO channel was reconstructed by embedding 3-D radiation patterns of the antennas into the propagation path estimates. Equivalently the channel simulations were performed with a quasi deterministic radio channel generator (QuaDRiGa) using the defined parameters. The channel capacity, Demmel condition number, and relative condition numbers are used as the comparison metrics between reconstructed and modeled channels. The results show that the reconstructed MIMO channel matches the simulated MIMO channel well.Tiivistelmä Tämä väitöskirja esittää parametroinnit kolmiulotteiselle geometriaan perustuvalle stokastiselle radiokanavamallille 10 GHz:n taajuusalueella perustuen mitattuun radiokanavaan. Väitöskirja koostuu kolmesta pääalueesta: radiokanavamittaukset, radiokanavamallin parametrien määrittäminen ja mallin validointi. Aluksi kuvataan kaksikerroksisessa aula ja kaupunkipiensolu ympäristöissä monilähetin monivastaanotin (MIMO) järjestelmällä tehdyt kanavamittaukset. Mittaukset tehtiin vektoripiirianalysaattorilla ja kaksoispolaroiduilla virtuaaliantenniryhmillä 500 MHz kaistanleveydellä. Mittausdata jälkikäsiteltiin käyttämällä ESPRIT-algoritmia ja jälkikäsitelty data varmennettiin osittain deterministisellä mittausympäristön karttaan pohjautuvalla radiokanavamallilla. Tulokset osoittivat hyvän yhteensopivuuden mitattujen ja mallinnettujen moniteiden välillä. Lisäksi toteuttiin yksi-lähetin yksi-vastaanotin mittaukset ulko-sisä etenemisympäristössä monikerroksisen lasin ja betoniseinän läpi. Tilastollinen analyysin avulla määritettiin täysi kolmiulotteinen kuvaus radioaallon etenemiskanavasta näköyhteys ja näköyhteydettömässä tilanteissa. Moniteiden suuremmista vaimennuksista johtuen viive ja kulmahajonnat ovat pienemmät verrattaessa matalempiin taajuuksiin. Peiliheijastus on diffuusisirontaa merkittävämpi radioaallon etenemismekanismi johtaen pienempiin klustereiden kulmahajeisiin matalempiin taajuuksiin verrattuna. Monikerroksisen lasin läpäisyvaimennus on samankaltainen kuin alemmilla taajuuksilla, kun sitä vastoin betoniseinän vaimennus on muutaman desibelin suurempi kuin alemmilla taajuuksilla. Lopulta geometriaan perustava stokastinen radiokanavamalli validoidaan määritellyillä parametreilla. MIMO kanava uudelleen rakennetaan lisäämällä kolmiulotteiset antennien säteilykuviot estimoituihin radioaallon etenemisteihin. Vastaavasti radiokanava simuloidaan näennäisesti deterministisellä radiokanavageneraattorilla (QuaDRiGa) käyttäen määriteltyjä mallin parametreja. Kanavakapasiteettia, Demmel ehtolukua ja suhteellista ehtolukua käytetään vertailumittareina uudelleen rakennetun ja simuloidun kanavan välillä. Tulosten perusteella uudelleen rakennettu MIMO kanava on yhteensopiva simuloidun radiokanavan kanssa

Interference study of micro licensing for 5G micro operator small cell deployments

Abstract 5G brings along very dense small cell deployments in specific locations such as hospitals, campuses, shopping malls, and factories. This will result in a novel 5G deployment scenario where different stakeholders, i.e., micro operators, are issued local spectrum access rights in the form of micro licenses, to deploy networks in the specific premises. This new form of sharing-based micro licensing guarantees that the local 5G networks remain free from harmful interference from each other and also protects potential incumbent spectrum users’ rights. It admits a larger number of stakeholders to gain access to the 5G spectrum to serve different vertical sectors’ needs beyond traditional mobile network operators (MNO) improving the competition landscape. We characterize the resulting interference scenarios between the different micro operators’ deployments and focus on the building-to-building scenario where two micro operators hold micro licenses in separate buildings in co-channel and adjacent channel cases. We analyze the resulting allowable transmit power levels of a base station from inside one building towards an end user mobile terminal inside another building as a function of the minimum separation distance between the two micro operator networks. Numerical results are provided for the example case of the 3.5 GHz band with different building entry losses characterizing the impact of propagation characteristics on the resulting interference levels. The results indicate that the building entry losses strongly influence the interference levels and resulting required minimum separation distances, which calls for flexibility in determining the micro license conditions for the building specific situation

System level analysis of multi-operator small cell network at 10 GHz

Abstract Due to higher cost and spectrum scarcity, it is expected that an efficient use of spectrum in fifth generation (5G) networks will rather rely on sharing than exclusive licenses, especially when higher frequency allocations are considered. In this paper, the performance of a dense indoor multi-operator small cell network at 10 GHz is analyzed. The main goal is to show the benefits obtained at higher carrier frequency due to network densification while mobile network operators are sharing the spectrum. The analysis is assessed through extensive system level simulations. The main performance metrics are user throughput and signal-to-interference-and-noise ratio. Results show that when 10 GHz carrier frequency is used it allows higher network densities while satisfying user throughput requirements. However, when network is sparse lower carrier frequency leads to better performance. When network is dense, on average 2 Mb/s better mean throughput is achieved at 10 GHz when compared to traditional cellular frequency