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Next-generation theranostics of brain pathologies with autonomous externally controllable nanonetworks: a trans-disciplinary approach with bio-nanodevice interfaces

Resultado final

Report on the theoretical communication models of EX transmitter

Model the stochastic diffusion of the EXs within the cytoplasm after encountering RF signals and the stochastic secretion of EXs out of the cell membrane. This will feed the design and model for Transmitter iNSC using circuit theory

Quantified analyses of impact of dissemination and communication measures 3

Quantified analyses of impact of dissemination and communication measures

Report on the validation of iR-NSCs and iM-NSC

Verify EX functional integrity with qPCR, proteomics and quantification of fluorescence.

Report on the theoretical communication models of EX receiver binding

Model the stochastic reception process of the EXs onto the GBM and their binding process to GBM enabling modelling of spatial binding process that is dependent on GBM surface shape and area

Project general report & updated plans 1

Project general report & updated plans

Kick-off meeting report & updated plans
Report on the prototype for 3D GBM tumour constructs

Culture GSCs neurospheres on electrospun nano-membranes with desired degradation rate. Assess progression to GBM structure with weekly readouts of histology and stemness vs. invasiveness biomarkers.

Updated Data Management Plan
Report on the theoretical communication models of EX propagation in the brain

Develop temporal and spatial diffusion model for the EX propagation within the brain and the fluidic drifts impact on EX propagation in neuronal tissue and in BBB Analyse the performance of EX propagation under varying parameters and environmental conditions This closedform analytical solution will be developed in coordination with the in vitro models in the first phase of the project under various parameters

Quantified analyses of impact of dissemination and communication measures 2

Quantified analyses of impact of dissemination and communication measures

Report on the autonomous and externally controllable MC system for the management of GBM

Asses and verify viability, stability, sustainability, effectiveness and robustness of the various system components with measurements of T5.1. Use the data to compare the optimal signal power vs the concentration of released EXs, and its impact on treatment and monitoring, serving to validate theoretical models of WP3 and the algorithms of T4.1.

Progress report on the simulator development

Simulator development based on the nanoNS3Sim Develop packages at the physical layer of the simulator including all elements from T31T34 and be optimized continually in conjunction with the in vitro experimental works

Final dissemination & exploitation plan
Quantified analyses of impact of dissemination and communication measures 4

Quantified analyses of impact of dissemination and communication measures

Quantified analyses of impact of dissemination and communication measures 1

Quantified analyses of impact of dissemination and communication measures

Project handbook
Project general report & updated plans 3

Project general report updated plans

Report on the viability of iNSCs and EXs In Vivo

Initially, inject fluorescently labelled EXs isolated from conditioned media of iRNSCs contralaterally in tumour -bearing animals. Assess migration and intracellular trafficking with daily intravital microscopy and weekly ex vivo fluorescent confocal microscopy over 6 weeks. Verify functional integrity with fluorescence quantification in brain and IDH1 miRNA upregulation in tumour cells. Identify Median Effective Dose (ED50) and correlate with iRNSCs numbers to be used in proof-of-concept studies.

Dissemination & exploitation plan
Report on the Central Unit including communication and intelligent algorithms

Enable and test the LRC and create the algorithms (deep learning convolution neural networks) and software to interface with the WBAN and perform tumour localization. Test the algorithm in vitro, using triple co-culture of T2.3 with and without tumour cells.

Report on in vivo efficacy of the reprogramming

Inject Rpf-GSCs stereotactically in RNU rats. Quantify and spatially analyse the fluorescence. Animals bearing vascularised tumours (5-6/group) will receive ipsilaterally: (i) iR-NSCs (treatment group); (ii) PBS (-ve control); (iii) iNSC expressing TRAIL (+ve control). Image in vivo daily until regression or death. Perform histology for regression and target protein readouts ex vivo. Isolate and characterize EXs from iR-NSC organoids cultures, animal models (serum and urine) as in T1.2.

Report on the proof-of-concept animal studies

Insert at least 3 devices to 3 groups of the models of D2.4 (5-6/group) via burred holes. Groups will receive additional implants as follows:(I) a reprogramming organoid; (II, positive control) iNSC expressing TRAIL (pro-apoptotic). (III, negative control), iNSCs without reprogramming miRNA. Daily measurements until regression or death: (i) distance between iR-NSCs and GBM; (ii) power and time required of RF for secretion, (iii) fluorescent signal at receiver. Histology will confirm if positive signal correlates with GBM recurrence.

Report on the deep learning algorithms and performance comparison for localization and prediction

Investigate deep learning algorithms, suitable for localizing the GBM. The selection will be highly dependent on the granularity of the data collected from monitoring EXs, in particular for (i) localizing accurately through triangulation using molecular signalling concentration, and (ii) predicting an accurate estimate of cell population before and after the treatment.

Data Management Plan
Updated &confirmed dissemination & exploitation plan 2

Updated confirmed dissemination exploitation plan

Project general report & updated plans 2

Project general report & updated plans

Public communication channels set-up
Report on in vitro efficacy of the reprogramming

Bring together co-cultures of EX-emitting iR-NSC and iM-NSCs organoids, BBB and GBM constructs in in vitro triple-culture system. Assess EX delivery across BBB with fluorescence readouts, proliferation markers, expression of target genes. Assess reprogramming efficacy of IDH1-miRNA with qPCR and GBM regression. Correlate NIR intensity from iM-NSCs with GBM cell viability and EX number.

Report on the end-to-end communication model

Integrate T31T33 in the endtoend capacity and delay model and analyse the performance of cell populations distances to GBM population and distribution of GBM niches as well as various environmental effects on the reliability of the EXs arriving with the required concentration Simulator development based on the nanoNS3Sim

Updated &confirmed dissemination & exploitation plan 1

Updated &confirmed dissemination & exploitation plan

Project general report & updated plans 4

Project general report updated plans 4

Simulator Framework and list of packages for nanoNS3Sim

Simulator development based on the nanoNS3Sim Develop packages at the physical layer of the simulator including all elements from T31T34 and be optimized continually in conjunction with the in vitro experimental works Make the simulator available as an Open Research Data Pilot

Publicaciones

On Mathematical Analysis of Active Drug Transport Coupled With Flow-Induced Diffusion in Blood Vessels

Autores: Hamidreza Arjmandi, Mohammad Zoofaghari, Seyed Vahid Rouzegar, Mladen Veletic, Ilangko Balasingham
Publicado en: IEEE Transactions on NanoBioscience, Edición 20/1, 2021, Página(s) 105-115, ISSN 1536-1241
Editor: Institute of Electrical and Electronics Engineers
DOI: 10.1109/tnb.2020.3038635

Bionanomachine Diagnostics and Nanonetwork Therapeutic in Brain Malignancies With Bionanodevice Interfaces

Autores: A. D. Odysseos and T. Nakano
Publicado en: IEEE Transactions on Molecular, Biological and Multi-Scale Communications, Edición vol. 8, no. 1, 2022, Página(s) 28-35, ISSN 2332-7804
Editor: IEEE
DOI: 10.1109/tmbmc.2021.3083725

Au nanostar nanoparticle as a bio-imaging agent and its detection and visualization in biosystems

Autores: E. Perevedentseva, N. Ali, Y.-C. Lin, A. Karmenyan, C.-C. Chang, O. Bibikova, I. Skovorodkin, R. Prunskaite-Hyyryläinen, S. J. Vainio, M. Kinnunen, C.-L. Cheng
Publicado en: Biomedical Optics Express, Edición 11/10, 2020, Página(s) 5872, ISSN 2156-7085
Editor: The Optical Society
DOI: 10.1364/boe.401462

A Voxel Model to Decipher the Role of Molecular Communication in the Growth of Glioblastoma Multiforme

Autores: H. Awan, S. Balasubramaniam and A. Odysseos
Publicado en: IEEE Transactions on NanoBioscience, Edición vol. 20, no. 3, 2021, Página(s) 296-310, ISSN 1536-1241
Editor: Institute of Electrical and Electronics Engineers
DOI: 10.1109/tnb.2021.3071922

Experimental Comparison of Primary and hiPS-Based In Vitro Blood–Brain Barrier Models for Pharmacological Research

Autores: Danz K, Höcherl T, Wien SL, Wien L, von Briesen H, Wagner S
Publicado en: Pharmaceutics, Edición 14(4), 2022, Página(s) 737-754, ISSN 1999-4923
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/pharmaceutics14040737

Computational estimation of chemical reaction rates in extracellular vesicle signaling

Autores: Damrath, M., Zoofaghari, M., Lekić, M., Rudsari, H. K., Pappalardo, F., Veletić, M., & Balasingham, I.
Publicado en: Nano Communication Networks, Edición 37, 2023, Página(s) 100455, ISSN 1878-7789
Editor: Elsevier BV
DOI: 10.1016/j.nancom.2023.100455

Trisk95 as Novel Skin Mirror for Normal and Diabetic Systemic Glucose Level

Autores: Nsrein Ali; Hamid Reza Rezvani; Diana Motei; Sufyan Suleman; Walid Mahfouf; Isabelle Marty; Veli-Pekka Ronkainen; Seppo Vainio; Seppo Vainio
Publicado en: Scientific Reports, Vol 10, Iss 1, Pp 1-17 (2020), Edición 21, 2020, ISSN 2045-2322
Editor: Nature Publishing Group
DOI: 10.1101/688887

Modeling of Modulated Exosome Release From Differentiated Induced Neural Stem Cells for Targeted Drug Delivery

Autores: Mladen Veletic, Michael Taynnan Barros, Hamidreza Arjmandi, Sasitharan Balasubramaniam, Ilangko Balasingham
Publicado en: IEEE Transactions on NanoBioscience, Edición 19/3, 2020, Página(s) 357-367, ISSN 1536-1241
Editor: Institute of Electrical and Electronics Engineers
DOI: 10.1109/tnb.2020.2991794

Synaptic Communication Engineering for Future Cognitive Brain–Machine Interfaces

Autores: M. Veletić and I. Balasingham
Publicado en: Proceedings of the IEEE, Edición vol. 107, no. 7, 2019, Página(s) 1425-1441, ISSN 0018-9219
Editor: Institute of Electrical and Electronics Engineers
DOI: 10.1109/jproc.2019.2915199

Biomedical applications of multifunctional magnetoelectric nanoparticles

Autores: Ehsanul Hoque Apu; Md Nafiujjaman; Srikumar Sandeep; Ashley V. Makela; Ali Khaleghi; Seppo Vainio; Christopher H. Contag; Jinxing Li; Ilangko Balasingham; Taeho Kim; Nureddin Ashammakhi
Publicado en: Materials Chemistry Frontiers, 2022, Página(s) 1368-1390, ISSN 2052-1537
Editor: Royal Society of Chemistry
DOI: 10.1039/d2qm00093h

Optimization of Extracellular Vesicle Release for Targeted Drug Delivery

Autores: Martin Damrath; Mladen Veletić; Hamid Khoshfekr Rudsari; Ilangko Balasingham
Publicado en: IEEE Transactions on NanoBioscience, 2023, ISSN 1536-1241
Editor: Institute of Electrical and Electronics Engineers
DOI: 10.1109/tnb.2023.3287637

Modeling and Simulations of Vascular-like Structure Formation of Cancer Cells

Autores: T. Tsuchiya, T. Saiki and T. Nakano
Publicado en: 2022 IEEE 16th International Symposium on Medical Information and Communication Technology (ISMICT), Edición 2022, 2022, Página(s) 1-6, ISBN 978-1-6654-7251-7
Editor: IEEE
DOI: 10.1109/ismict56646.2022.9828353

Optically Active Bionanomachine Interfaces Build Therapeutic Nanonetworks for Glioblastoma Multiforme

Autores: El Hamidieh A, Dietis N, Samoylenko A, Meiser I, Nicolaou N, Abdelrady E, Zhyvolozhnyi A, Vainio S, Odysseos AD.
Publicado en: 2022 IEEE 16th International Symposium on Medical Information and Communication Technology (ISMICT), Edición 2022, 2022, Página(s) 1-6
Editor: IEEE
DOI: 10.1109/ismict56646.2022.9828125

1-Bit Reconfigurable Phase Shifter for mm-Wave Antenna Beam-Steering Applications

Autores: A. Bilal, A. Quddious, A. Kanno, T. Kawanishi, M. A. Antoniades and S. Iezekiel
Publicado en: 2023 IEEE International Symposium on Antennas and Propagation and USNC-URSI Radio Science Meeting (USNC-URSI), 2023, Página(s) 1643-164, ISBN 9781665442282
Editor: IEEE
DOI: 10.1109/usnc-ursi52151.2023.10238025

Conformal Rat Head Wearable Antenna for Transcranial RF Stimulation

Autores: A. Quddious, A. Bilal, C. Pitris, A. D. Odysseos and S. Iezekiel
Publicado en: 2023 IEEE MTT-S International Microwave Biomedical Conference (IMBioC), 2023, Página(s) 169-171, ISBN 978-1-6654-9217-1
Editor: IEEE
DOI: 10.1109/imbioc56839.2023.10304886

Predator-Prey Adaptive Control for Exosome-based Molecular Communications Glioblastoma Treatment

Autores: C. Fonseca, M. T. Barros, A. Odysseos and S. Balasubramaniam
Publicado en: CC 2021 - IEEE International Conference on Communications, Edición 2021, 2021, Página(s) 1-7
Editor: IEEE
DOI: 10.1109/icc42927.2021.9500631

Extracellular vesicle propagation in acidic tumor microenvironment

Autores: Milica Lekic; Mohammad Zoofaghari; Mladen Veletic; Ilangko Balasingham
Publicado en: NANOCOM '22: Proceedings of the 9th ACM International Conference on Nanoscale Computing and Communication, Edición 3, 2022
Editor: Association for Computing Machinery
DOI: 10.1145/3558583.3558843

Growing Bio-nanomachine Networks: Application to Malignant Tumor Evolution and Progression

Autores: Tadashi Nakano, Yutaka Okaie, Nikolaos Dietis, Andreani D. Odysseos
Publicado en: GLOBECOM 2020 - 2020 IEEE Global Communications Conference, 2020, Página(s) 1-6, ISBN 978-1-7281-8298-8
Editor: IEEE
DOI: 10.1109/globecom42002.2020.9322529

A Molecular Communication Model of Exosome-mediated Brain Drug Delivery

Autores: Mladen Veletić, Michael Taynnan Barros, Ilangko Balasingham, Sasitharan Balasubramaniam
Publicado en: Proceedings of the Sixth Annual ACM International Conference on Nanoscale Computing and Communication - NANOCOM '19, 2019, Página(s) 1-7, ISBN 9781-450368971
Editor: ACM Press
DOI: 10.1145/3345312.3345478

EBG-Backed Head Wearable Antenna Array for Transcranial Radio-Frequency Stimulation Applications

Autores: Abdul Quddious; Asif Bilal; Andreani D. Odysseos; Constantinos Pitris; Stavros Iezekiel
Publicado en: 2023 IEEE International Symposium on Antennas and Propagation and USNC-URSI Radio Science Meeting (USNC-URSI), 2023, Página(s) 1269-1270, ISBN 9781665442282
Editor: IEEE
DOI: 10.1109/usnc-ursi52151.2023.10237498

An autonomous electronics system for ultrasound energy transfer and passive communication

Autores: M. Fournelle, A. Fadel, F. -J. Becker, M. Moses, M. Schmieger and S. Tretbar
Publicado en: 2022 IEEE International Ultrasonics Symposium (IUS), Edición 2022, 2022, Página(s) 1-4
Editor: IEEE
DOI: 10.1109/ius54386.2022.9958097

Analysis of Molecular Communications on the Growth Structure of Glioblastoma Multiforme

Autores: Hamdan Awan; Andreani Odysseos; Niovi Nicolaou; Sasitharan Balasubramaniam
Publicado en: 2021 IEEE Global Communications Conference (GLOBECOM), Edición 2021, 2021, Página(s) 1-6
Editor: IEEE
DOI: 10.1109/globecom46510.2021.9685860

Quasi-spherical absorbing receiver model of glioblastoma cells for exosome-based molecular communications

Autores: Fonseca, Caio and Barros, Michael Taynan and Odysseos, Andreani and Kidambi, Srivatsan and Balasubramaniam, Sasitharan
Publicado en: Proceedings of the 9th ACM International Conference on Nanoscale Computing and Communication, Edición 2022, 2022, Página(s) 1-8, ISBN 9781450398671
Editor: Association for Computing Machinery
DOI: 10.1145/3558583.3558864

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