Project

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Transport of nanoparticles after release from a biodegradable implant

English title Transport of nanoparticles after release from a biodegradable implant
Applicant Frenz Martin
Number 131297
Funding scheme NRP 64 Opportunities and Risks of Nanomaterials
Research institution Institut für angewandte Physik Universität Bern
Institution of higher education University of Berne - BE
Main discipline Biophysics
Start/End 01.05.2011 - 31.12.2015
Approved amount 635'544.00
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All Disciplines (2)

Discipline
Biophysics
Cellular Biology, Cytology

Keywords (7)

nanoparticles; encapsulation; toxicity; cellular uptake; pharmacokinetics; biodistribution; implant

Lay Summary (English)

Lead
Lay summary
Nanotechnology is an enabling technology with an enormous impact on many of the currently emerging medical applications such as diagnosis, therapy and prevention of human disease and disorders. Nanotechnology is foreseen to change health care in a fundamental way. One of such application is laser tissue soldering, a kind of tissue fusion which allows to tightly seal surgical wounds and in particular vascular lesions. It is based on a heat induced denaturation process of proteins like bovine serum albumin (BSA), providing the necessary acute tissue strength. This novel tissue fusion technique is perceived as a minimally invasive alternative to the classical use of suture or stitches to close lacerations, which is a powerful perspective in many open and endoscopic surgical applications. It provides essential advantages over traditional suturing including speed, immediate liquid tightness, reduced tissue trauma and faster healing thus reducing the exposure of the patients. This novel laser assisted anastomoses technique will open doors for new avenues of surgical applications especially in neurosurgery where operation time is one crucial parameter. As one major application tissue soldering will be used for cerebral bypass surgery as well as cranial closure techniques. Laser tissue soldering involves the combination of near-infrared radiation, which deeply penetrates tissue, with a biodegradable scaffold in which an exogenous chromophore as heat transducer is embedded e.g. gold nanoparticles (10-80 nm in diameter) or core shell silica nanoparticles (30 -100 nm) containing an encapsulated, ICG dye. The chromophore or gold nanoparticles selectively and locally convert the laser radiation into heat. Over time during the healing process, the biodegradable scaffold will break down releasing the embedded nanoparticles into the surrounding tissue and probably also into the blood stream. The main goal of the project therefore is to determine the nanoparticle biodistribution and their toxicokinetic properties in cell cultures, tissue slices and in vivo. Hereto, we will first study the influence of laser irradiation on the stability and on the physicochemical properties of the nanoparticles since they determine the amount and the pathway of the cellular uptake of the nanoparticles. In a second step we will analyze the mobility and biodistribution of the nanoparticle in brain tissue in vivo i.e. the take-up by the surrounding tissue, the blood stream, and different organs such as liver, spleen, thymus and cervical lymph nodes on a cellular level. In order to track the nanoparticles two approaches will be followed.1. Use of highly sophisticated methods e.g. two photon microscopy, fluorescence correlation spectroscopy, confocal microscopy, AFM and transmission electron microscopy (TEM) to fully characterize the nano-particals prior and after laser irradiation and to analyze histological sections.2. Core shell nanoparticles containing a 14C radiotracer and/or sensitive fluorochrome or a spin label, but exhibiting the same surface properties and size distribution like the ICG doped particles will be monitored by scintillation counting, fluorescences or ESR techniques. Together with the above mentioned investigations, follow-up in-vivo experiments will allow evaluating possible health risks and will enable public health officials in Switzerland and elsewhere to better use current results in making decisions about nanoparticles regulations.The project involves partners from five different Institutes having complementary expertise and establishes a close interdisciplinary research cooperation. Following questions will be addressed: Do nanoparticle change their properties under laser irradiation and how does this affect their interaction with biological tissue? How do the nanoparticles distribute in the adjacent tissue, organs, blood stream or cells after degradation of the scaffold and can any cellular inflammatory responses or adverse effects on the surrounding tissue or organs be detected?Within the three years period of the envisaged project, the following discoveries are expected to be delivered:1. Basic information on particle transport mechanisms in extracellular spaces 2. Mobility and biodistribution of nanoparticles after therapeutic intervention 3. Toxicity of the nanoparticles used for laser assisted tissue soldering.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Silica nanoparticle-exposure during neuronal differentiation modulates dopaminergic and cholinergic phenotypes in SH-SY5Y cells
Wiedmer Linda, Ducray Angélique D., Frenz Martin, Stoffel Michael H., Widmer Hans-Rudolf, Mevissen Meike (2019), Silica nanoparticle-exposure during neuronal differentiation modulates dopaminergic and cholinergic phenotypes in SH-SY5Y cells, in Journal of Nanobiotechnology, 17(1), 46-46.
Effects of silica nanoparticle exposure on mitochondrial function during neuronal differentiation.
Ducray Angélique D, Felser Andrea, Zielinski Jana, Bittner Aniela, Bürgi Julia V, Nuoffer Jean-Marc, Frenz Martin, Mevissen Meike (2017), Effects of silica nanoparticle exposure on mitochondrial function during neuronal differentiation., in Journal of nanobiotechnology, 15(1), 49-49.
Uptake of silica nanoparticles in the brain and effects on neuronal differentiation using different in vitro models.
Ducray Angélique D, Stojiljkovic Ana, Möller Anja, Stoffel Michael H, Widmer Hans-Rudolf, Frenz Martin, Mevissen Meike (2017), Uptake of silica nanoparticles in the brain and effects on neuronal differentiation using different in vitro models., in Nanomedicine : nanotechnology, biology, and medicine, 13(3), 1195-1204.
Evaluation of endocytosis of silica particles used in biodegradable implants in the brain.
Zielinski Jana, Möller Anja-Maria, Frenz Martin, Mevissen Meike (2016), Evaluation of endocytosis of silica particles used in biodegradable implants in the brain., in Nanomedicine : nanotechnology, biology, and medicine, 12(6), 1603-13.
Nanoparticles for laser tissue soldering in the brain - chances and risks. An interdisciplinary research project
Möller Anja Maria, Mevissen Meike, Frenz Martin (2015), Nanoparticles for laser tissue soldering in the brain - chances and risks. An interdisciplinary research project, in Bulletin VSH-AEU, 41(1/2), 80-83.
An in vitro toxicity evaluation of gold-, PLLA- and PCL-coated silica nanoparticles in neuronal cells for nanoparticle-assisted laser-tissue soldering
Koch Franziska, Möller Anja Maria, Frenz Martin, Pieles Uwe, Kuehni-Boghenbor Kathrin, Mevissen Meike (2013), An in vitro toxicity evaluation of gold-, PLLA- and PCL-coated silica nanoparticles in neuronal cells for nanoparticle-assisted laser-tissue soldering, in Toxicology in Vitro, 28(5), 990-998.
Indocyanine green loaded biocompatible nanoparticles: Stabilization of indocyanine green (ICG) using biocompatible silica-poly(ε-caprolactone) grafted nanocomposites
Schönbächler Andrea, Gleied Olfa, Huwyler Jörg, Frenz Martin, Pieles Uwe (2013), Indocyanine green loaded biocompatible nanoparticles: Stabilization of indocyanine green (ICG) using biocompatible silica-poly(ε-caprolactone) grafted nanocomposites, in Journal of Photochemistry and Photobiology A: Chemistry, 261, 12-19.
Tissue fusion: a new opportunity for sutureless bypass surgery
Bogni Serge, Schöni Daniel, Constantinescu Mihai, Wirth Amina, Vajtai Istvan, Bregy Amadé, Raabe Andreas, Pieles Uwe, Frenz Martin, Reinert Michael (2012), Tissue fusion: a new opportunity for sutureless bypass surgery, in Tetsuya TsukaharaLuca RegliDaniel HänggiBernd TurowskiHans-Jakob Steiger (ed.), Springer, Wien, New York, 45-52.
Polycapsulated Silica Core Nanoparticles for Laser Tissue Soldering
Schönbächler Andrea, Andereggen Lukas, Möller Anja, Marti Dominik, Guldimann Claudia, Widmer Hans-Rudolf, Mevisen Meike, Frenz Martin, Reinert Michael, Polycapsulated Silica Core Nanoparticles for Laser Tissue Soldering, in J Neurol Surg A Cent Eur Neurosurg.

Collaboration

Group / person Country
Types of collaboration
STORZ Endoskop Produktions GmbH, Schaffhausen Germany (Europe)
- Industry/business/other use-inspired collaboration
Prof. M.H. Stoffel, Division Veterinary Anatomy, Universität Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Francesco Stellacci, SUNMIL, Institut des matériaux, EPFL - STI – IMX, CH-1015 Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Christoph Weder, Adolphe Merkle Institute, Université de Fribourg, CH-1723 Marly 1 Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. H.R. Widmer, Neurochirurgie Insel Spital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
VetPham Symposium Talk given at a conference Biodistribution and effects of silica nanoparticles exposure in organotypic rat hippocampal slice cultures and dissociated cultures 01.10.2015 Hannover, Germany Frenz Martin; Möller Anja-Maria;
SNI Annual Meeting Talk given at a conference Laser Tissue Soldering,new ways for minimal invasive surgery 11.09.2015 Lenzerheide, Switzerland Frenz Martin; Gmür Samira; Buchs Andrea; Leisibach Andrea; Pieles Uwe;
NanoBioTech Talk given at a conference Biocompatible hybrid core shell nanoparticles as delivery system for indocyanine green for laser tissue soldering 18.11.2014 Montreux, Switzerland Pieles Uwe; Frenz Martin; Buchs Andrea;
VETPHARM Talk given at a conference Laser tissue soldering using nanoparticles in a biodegradable implant. Uptake of two types of silica nanoparticles in murine microglial and human neuron-like cells and rat organotypic hippo-campal slices 11.09.2014 Zürich, Switzerland Frenz Martin; Möller Anja-Maria; Pieles Uwe; Leisibach Andrea;
Biomedical Photonics Network Talk given at a conference Electrospinning: A novel application for tissue soldering 01.11.2013 Bern, Switzerland Frenz Martin; Buchs Andrea; Möller Anja-Maria; Pieles Uwe;
CLINAM2013 Talk given at a conference Transport of Nanoparticles after release from a biodegradable implant 25.06.2013 Basel, Switzerland Möller Anja-Maria; Pieles Uwe; Frenz Martin; Buchs Andrea;
RMS Foundation Individual talk Laser-tissue-soldering using NP-modified polycaprolactone electrospun scaffolds 24.04.2013 Bettlach, Switzerland Frenz Martin;
Biologisierung der Medizintechnik, Workshop III, NMI Innovationsforum Talk given at a conference Nanostrukturierte resorbierbare Polymere zur endoskopischen Gewebeverbindung 22.11.2012 Reutlingen, Germany Frenz Martin;
International Conference on Bioinspired and Biobased Chemistry & Materials Talk given at a conference Biocompatible silica nanomaterials grafted amphiphilic block copolymer conjugated with indocyanine green 03.10.2012 Nice, France Pieles Uwe; Buchs Andrea; Frenz Martin;
MipTech Poster Biocompatible Silica Nanomaterials grafted Block Copolymer Poly (ε-Caprolactone)-b-Poly (L-Lactide) conjugated with Indocyanine Green 27.09.2012 Basel, Switzerland Buchs Andrea; Frenz Martin; Pieles Uwe;
International Symposium on Biomedicine and Drug-Development - Nanotechnology: from Bench to Enduser Talk given at a conference Mechanism of nanoparticle-mediatedphotomechanical cell damage 25.09.2012 Basel, Switzerland Frenz Martin;
7th International Summer School on Advanced Biotechnology Talk given at a conference Electrospinning of a nanoparticle-doped polycaprolactone scaffold for laser tissue soldering 10.09.2012 Santa Margherita di Belice, Italy Pieles Uwe; Frenz Martin; Buchs Andrea;
ALT'12 conference Talk given at a conference Laser tissue soldering using nanoparticle-doped electrospun polycaprolactone scaffolds 02.09.2012 Thun, Switzerland Möller Anja-Maria; Pieles Uwe; Frenz Martin; Buchs Andrea;
Swiss Physical Society Talk given at a conference Targeting cells with gold nanoparticles 22.07.2012 Zürich, Switzerland Frenz Martin;
Colloids and Nanomedicine 2012 Poster Biocompatible Nanoparticle Delivery System for Indocyanine Green: Synthesis and Study of Si@PCL-b-PLLA Conjugated with ICG 15.07.2012 Amsterdam, Netherlands Buchs Andrea; Pieles Uwe; Frenz Martin;
Clinam, European Summit for Clinical Nanomedicine Poster Biocompatible Nanoparticles Delivery System for Indocyanine Green: Synthesis and Study of Nanocomposites Based ICG- Poly (ε-Caprolactone) and Poly (L-Lactide) Grafted from the Silica Surface 09.05.2012 Basel, Switzerland Frenz Martin; Buchs Andrea; Pieles Uwe; Reinert Michael;
PolyColl 2012 Poster Biocompatible Silica Nanomaterial Grafted Amphiphilic Block Copolymer conjugated with Indocyanine Green 20.04.2012 Fribourg, Switzerland Frenz Martin; Pieles Uwe; Buchs Andrea;
BIOS - Photonics West, SPIE Talk given at a conference Nanoparticle supported laser-tissue-soldering for closure of natural orificies for transluminal endoscopic surgery 20.01.2012 San Francisco, United States of America Pieles Uwe; Reinert Michael; Frenz Martin; Buchs Andrea;
Annual meeting of the Biomedical Photonics Network Poster Tissue soldering with nano particle scaffold 30.11.2011 Neuenburg, Switzerland Reinert Michael; Frenz Martin;
3rd International Symposium "Topical problems of biophotonics - 2011" Talk given at a conference Laser-tissue soldering using ICG loaded silica nanoshelle 20.07.2011 Nizhny Novgorod, Russia Pieles Uwe; Reinert Michael; Frenz Martin;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Nanotechnologie: Was bringt sie uns? Performances, exhibitions (e.g. for education institutions) 16.10.2014 Bern, Switzerland Frenz Martin;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Nanopartickel in der Theranostik Western Switzerland 2017
Talks/events/exhibitions Nanotechnologie - Faszination oder Gefahr? Western Switzerland 2015

Awards

Title Year
3. Ypsomed Innovationspreis "Nanostrukturiertes biodegradierbares Polymer für das endoskopische Laser Gewebe Soldering" 2012

Abstract

Nanotechnology is an enabling technology with an enormous impact on many of the currently emerging medical applications such as diagnosis, therapy and prevention of human disease and disorders. Nanotechnology is foreseen to change health care in a fundamental way. One of such application is laser tissue soldering, a kind of tissue fusion which allows to tightly seal surgical wounds and in particular vascular lesions. It is based on a heat induced denaturation process of proteins like bovine serum albumin (BSA), providing the necessary acute tissue strength. This novel tissue fusion technique is perceived as a minimally invasive alternative to the classical use of suture or stitches to close lacerations, which is a powerful perspective in many open and endoscopic surgical applications. It provides essential advantages over traditional suturing including speed, immediate liquid tightness, reduced tissue trauma and faster healing thus reducing the exposure of the patients. This novel laser assisted anastomoses technique will open doors for new avenues of surgical applications especially in neurosurgery where operation time is one crucial parameter. As one major application tissue soldering will be used for cerebral bypass surgery as well as cranial closure techniques. Laser tissue soldering involves the combination of near-infrared radiation, which deeply penetrates tissue, with a biodegradable scaffold in which an exogenous chromophore as heat transducer is embedded e.g. gold nanoparticles (10-80 nm in diameter) or core shell silica nanoparticles (30 -100 nm) containing an encapsulated, ICG dye. The chromophore or gold nanoparticles selectively and locally convert the laser radiation into heat. Over time during the healing process, the biodegradable scaffold will break down releasing the embedded nanoparticles into the surrounding tissue and probably also into the blood stream. The main goal of the project therefore is to determine the nanoparticle biodistribution and their toxicokinetic properties in cell cultures, tissue slices and in vivo. Hereto, we will first study the influence of laser irradiation on the stability and on the physicochemical properties of the nanoparticles since they determine the amount and the pathway of the cellular uptake of the nanoparticles. In a second step we will analyze the mobility and biodistribution of the nanoparticle in brain tissue in vivo i.e. the take-up by the surrounding tissue, the blood stream, and different organs such as liver, spleen, thymus and cervical lymph nodes on a cellular level. In order to track the nanoparticles two approaches will be followed.1. Use of highly sophisticated methods e.g. two photon microscopy, fluorescence correlation spectroscopy, confocal microscopy, AFM and transmission electron microscopy (TEM) to fully characterize the nano-particals prior and after laser irradiation and to analyze histological sections.2. Core shell nanoparticles containing a 14C radiotracer and/or sensitive fluorochrome or a spin label, but exhibiting the same surface properties and size distribution like the ICG doped particles will be monitored by scintillation counting, fluorescences or ESR techniques. Together with the above mentioned investigations, follow-up in-vivo experiments will allow evaluating possible health risks and will enable public health officials in Switzerland and elsewhere to better use current results in making decisions about nanoparticles regulations.The project involves partners from five different Institutes having complementary expertise and establishes a close interdisciplinary research cooperation. Following questions will be addressed: Do nanoparticle change their properties under laser irradiation and how does this affect their interaction with biological tissue? How do the nanoparticles distribute in the adjacent tissue, organs, blood stream or cells after degradation of the scaffold and can any cellular inflammatory responses or adverse effects on the surrounding tissue or organs be detected?Within the three years period of the envisaged project, the following discoveries are expected to be delivered:1. Basic information on particle transport mechanisms in extracellular spaces 2. Mobility and biodistribution of nanoparticles after therapeutic intervention 3. Toxicity of the nanoparticles used for laser assisted tissue soldering.
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