Workshop 4 Transversal themes linked to health

Workshop 4 Transversal themes linked to health
Speakers
• NOW: Ozlem YESIL CELIKTAS ‐ Ege University
• NEXT: Yağız Üresin – Univ of Istanbul
Formulation of a nanomedicine
targetting neuroblastoma
An offer to be fitted in a consortium
Ozlem YESIL-CELIKTAS
Ege University
Bioengineering Department
Izmir, Turkey
[email protected]
+90 232 388 49 55
DESCRIPTION
Our research group studied the cytotoxic effects of some cyanidin
containing matrices on estrogen dependent and independent breast
cancer, colon, prostate and brain tumor cell lines and also VERO
healthy cell line.
Some promising results have been obtained particularly on brain
tumor cell lines. And recently focusing on different extraction and
encapsulation techniques in order to cope with blood-brain barrier
restrictions.
Therefore our main interest is to join an existing consortium or to
establish one in order to formulate a nanomedicine targetting
neuroblastoma along with creating an understanding of the
mechanism.
SKILLS OFFERED
- Isolation of biomolecules by different separation processes
- Encapsulation of biomolecules using various techniques such as
sol-gel, supercritical fluids, formation of niosome and emulsion
- Immobilization of biomolecules to microreactors
MAIN TOPICS OF INTREST
- Molecular mechanism
- Modelling
- Microfluidics
NOVEL FLUIDIC TECHNOLOGIES AND APPLICATIONS
Size Distribution by Volume
50
Volume (%)
40
30
20
10
0
0.1
1
10
100
1000
Size (d.nm)
Record 31: R1.1 1
Research Interests
 separation of value-added compounds
such as enzymes and secondary metabolites,
 encapsulation of drug molecules and
Proteins to develop micro-/nano particles,
 enzyme treatments and drying of
scaffolds using supercritical fluids
 microfluidics and microreactor applications with a
focus on sol-gel technology
Record 32: R1.1 2
Record 33: R1.1 3
10000
INTERNATIONAL PROJECTS
 Sustainable Polymers from Algae Sugars and
Hydrocarbons (SPLASH). Funded by EU FP7, Contact for
Turkish partner, (2012-2016). (A consortium of 20 partners
of which 55% are SMEs)
 Enzymatic reactions in micro devices with a focus on
sol-gel technology: experimental study and model
development. Funded by TUBITAK (112M249) & BMBF,
Project Coordinator, (2014-2016). (Bilateral cooperation
between Ege University and Technical University of
Hamburg-Harburg)
 Fundamentals for synthetic biological systems (SynBio);
Joachim Herz Stiftung & LandesexzellenzinitiativeHamburg projesi, Araştırmacı (Temmuz-Eylül 2012)
Speakers
• NOW: Yağız Üresin – Univ of Istanbul
• NEXT: Helena Azevedo – Queen Mary Univ
Drug Development
Prof. Dr. Yağız Üresin
Drug Development
Current projects
• Clinical Research Excellence Center
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Early phase trials
Translational medicine
Bioequivalence
Biosimilarity
– Partnerships: Zurich University
Drug Development
Drug Repositioning Request
• ITAM/ISTKA funded project
• Tubitak project on cognitive impairment passed 1st phase of approval
• EU RISE project submitted
• What we offer:
– Large patient population, already diagnosed in 1 of our 5 research hospitals – Clinical trial infrastructure, regulation & ethics know‐how, genomics lab, drug repositioning experience, strong relations with MoH, reimbursement authority & pharma industry
• Looking for EU partnerships on
– Cognitive impairment – Rare diseases/orphan drugs
Drug Development
Clinical trial • Clinical Research Excellence Center
• 5 research hospitals with long years’ experience on several clinical phase trials
Drug Development
• We have enough human resources
• The Clustering Support Program ‐ The Technology Transfer Center of Istanbul University
• We need international partnerships
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Horizon 2020
IMI
RISE Academic ‐ industrial partnerships
Speakers
• NOW: Helena Azevedo – Queen Mary Univ
• NEXT: Francesco Turci – Univ of Torino
An integrative materials partner: molecular engineering, hierarchical structure, and computational modelling
Helena Azevedo, Alvaro Mata, Lorenzo Botto
School of Engineering and Materials Science
Queen Mary, University of London
http://www.sems.qmul.ac.uk/
Contact details:
Tel: +44 (0)20 7882 5282 | Email: [email protected]
Tel: +44 (0)20 7882 6279 | Email: [email protected]
Tel: +44 (0)20 7882 7503 | Email: [email protected]
About what we do
Molecular Engineering
Hierarchical
Control
Device/Material
Properties
Simulation/
modelling
Potential Applications
Injectable scaffolds
Tissue grafts
Cell therapies
Non‐union fracture
Theracellinc.com
Tissue engineering
Drug discovery
Seifalian Lab, UCL
Technewslit.com
Biomaterials engineering: molecular design
Molecular design: biomaterials with intrinsic functionality
Peptides (small molecules; molecular recognition) Building blocks
Macromolecules (large molecules; structural function) Molecular self‐assembly: biomaterials with nanoscale organization
Peptides
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•
•
•
Simple structural and signalling building blocks
Unparalleled bioactivity
Easily synthesized
Can be easily tuned for a specific application
5 mm
KNOW‐HOW TECHNOLOGY
BUILDING BLOCKS
About what we can offer
 Peptide synthesis capabilities (purity >95%)
 Peptides for applications in biomaterials design and therapies (self‐ assembling peptides, linear or cyclic peptides, targeting peptides,
peptide discovery by phage display)
 Macromolecules (hyaluronan, elastin, collagen, block copolymers)
 Microfabrication techniques for hierarchical biomaterials
 Responsive biomaterials
 Biomimetic materials (cartilage, bone, disc, skin, ....)
 Multiscale computational and mathematical modelling to understand
mechanics of soft biological materials
About what we are looking for
We will coordinate 2 proposals on the following calls (Health and NMP)
• PHC‐16 2015: Tools and Technologies for Advanced Therapies • NMP 12‐2015: Biomaterials for treatment and prevention of Alzheimer's disease
 We are looking for partners with complementary expertise to participate
in the above calls We are interested in participate/contribute to proposals in the call:
• NMP 11‐2015: Nanomedicine therapy for cancer
Speakers
• NOW: Francesco Turci – Univ of Torino
• NEXT: Ling Peng‐ AMU/CNRS
The Department of Chemistry at University of Torino Chemistry @ UniTO
We offer skills for:
•NMP 11‐2015: Nanomedicine therapy for cancer
•PHC 11–2015: Development of new diagnostic tools and technologies: in vivo medical
imaging technologies
•PHC 16–2015: Tools and technologies for advanced therapies
and request specific expertise for:
•PHC 16–2015: Tools and technologies for advanced therapies
PHC 11–2015: Development of new diagnostic tools and technologies: in vivo medical imaging technologies
OFFER:
•
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Lead a WP on the preparation, surface functionalization and investigation of the interaction with biomolecules, in media relevant for in‐vitro and in‐vivo applications, of highly bright hybrid dye‐silica nanoparticles for optical imaging
Lead a WP on the synthesis of fluorescent bioactive analogues of Strigolactones to be used as biological probes
PHC 16–2015: Tools and technologies for advanced therapies REQUEST (for a proposal on the preparation of hernia‐repair adhesive meshes):
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synthesis and characterization of polymeric materials for biomedical applications
surface treatments (dip coating, electrospinning)
in vitro tests for evaluating the response of adhesive meshes prepared
OFFER:
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in vitro pre‐clinical studies with artificial hydrophilic and/or lipophilic membranes and biological models (ex vivo and artificial skin or mucosa)
Cellular and cell‐free tests can be performed to evaluate a) the physico‐chemical properties regulating the interaction of the enhancer with the biological environment,
the synthesis and characterization of paramagnetic metal complexes with pharmacological potential in the solid state and in solution
lead a work package on the formulation of functionalized bioactive glasses to be used as carriers for the development of a pH‐stimuli responsive biomaterials for bone diseases
synthesis of fluorescent bioactive analogues of Strigolactones
NMP 11‐2015: Nanomedicine therapy for cancer
OFFER:
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synthesis and characterization of paramagnetic metal complexes with pharmacological potential in the solid state and in solution;
synthesis of fluorescent bioactive analogues of Strigolactones;
develop and characterize theranostic agents exploitable for therapy follow‐up by MRI or Optical Imaging;
develop innovative photodynamic therapy with an integrated set of techniques for the evaluation of the photoactivity of nanomaterials
The Department of Chemistry at University of Torino (Chemistry@UniTO) participates in the EU strategic research agenda since the 4th Framework Programme (FP4).
Chemistry@UniTO is currently involved in 20 EU projects funded under the FP7, with a total budget of ca. 5 M€. Recent projects include 9 international Cooperation projects (mainly NMP and ENERGY), 6 People and 3 Capacities.
Dr. Francesco Turci
[email protected] / [email protected]
+39 011 670.7577 / +39 348 573.4293
Speakers
• NOW: Ling Peng‐ AMU/CNRS
• NEXT: Olivier Sandre – Univ
Bordeaux/CNRS/IPB Dendrimer nanotechnology based drug delivery
for treating diseases Dr. Ling PENG
Centre Interdisciplinaire de Nanosceince de Marseille Aix‐Marseille University ‐ CNRS
France
Our offer: Functional dendrimer nanovectors for drug delivery
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Nucleic acid delivery in RNAi‐based therapy
disease models: cancer, HIV, diabete, Parkinson disease
in vitro models: cancer cells, primary cells and stem cells
in vivo models: mice, rat, rodants and non‐rodants
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Anticancer drug delivery in cancer therapy
Pancreatic, prostate, breast, ovarian and brain cancer
Our project: Dendrimer nanotechnology based drug delivery
for treating diseases • PHC 14 – 2015: New therapies for rare diseases
• PHC 16 ‐2015: Tools and technologies for advanced therapies
• NMP 11‐2015: Nanomedicine therapy for cancer
• NMP 12‐2015: Biomaterials for treatment and prevention of Alzheimer's disease
Dr. Ling PENG
Centre Interdisciplinaire de Nanosceince de Marseille
Aix‐Marseille University – CNRS
ling.peng@univ‐amu.fr
Tel: 00 33 (4) 9182 9154
00 33 (6) 1724 8164
Speakers
• NOW: Olivier Sandre – Univ
Bordeaux/CNRS/IPB • NEXT: Volunteers possible if time Polymer Self-assembly and Life Sciences
Sébastien Lecommandoux, J.F. Le Meins, C. Schatz, E. Garanger, O. Sandre
Université de Bordeaux
Laboratoire de Chimie des Polymères Organiques,
CNRS - ENSCBP – University of Bordeaux
Pessac, France
[email protected]
[email protected] www.lcpo.fr
Polymer Self‐assembly and Life Sciences research team
24 active research staff, including 6 permanent researchers, 8 PhDs, 5 postdocs, 5 Master‐2
S. Lecommandoux (PR)
Group Leader
O. Sandre (DR)
Nano‐biomagnetism
C. Schatz (MCF)
Polysaccharides
E. Garanger (CR)
Peptides
J.‐F. Le Meins (MCF)
Hybrid membranes
E. Ibarboure (IE)
Microcopies
Polymer Self‐assembly and Life Sciences
“Know‐How”
Synthesis of amphiphilic block copolymers (based on polypeptides, polysaccharides
and proteins)
Bioconjugation & biofunctionalization ‐ Targeting (peptide, antibody)
‐ Fluorescence labelling
‐ MR contrast agent incorporation
Drug loading &
controlled release
‐ of drugs, peptides, nucleic acids
‐ using pH, T, hyperthermia
Block copolymer self‐assembly (directed self‐assembly, emulsification, microfluidic, coacervation)
Colloidal characterization
Polymer
nanoparticles
‐ Scattering (DLS, SLS, SANS)
‐ Zetametry
‐ Viscometry, rheology
‐ Fluo/confocal microscopies
‐ Microcalorimetry, ITC
‐ Imaging (TEM, AFM)
‐ Magnetic properties
Preparation of samples for preclinical studies
“clean lab” (laminar flow hood)
interaction with serum
interaction with model membranes…
 Drug‐delivery, controlled release of actives (cosmetics, personal care and pharma)
 Bio‐imaging and theranostics
 Virus and cell mimics, nano/micro‐(bio)reactors (enzymes,…)
From polymer chemistry and self‐assembly to nanomedicine
AMPHIPHILIC POLYPEPTIDE AND SACCHARIDE-BASED BLOCK COPOLYMERS
RING-OPENING POLYMERIZATION
Macroinitiator
ROP
of
NCA
Polymer
segment
BIOCONJUGATION
Synthetic block
Natural segment
“click”
PROTEIN ENGINEERING
Recombinant DNA
Production
in E. coli
Polypeptide
Biomacromolecule
Peptide, Protein
Oligo-/Polysaccharide
(VPGX1G)n-b-(VPGX2G)m
Multifunctional and bioactive polymersomes for cancer imaging and therapy
- Passive targeting (EPR)
- Active targeting (Peptide,
Antibody, Magnetic attraction)
- Controlled drug-release
(Stimuli-responsive using pH, T°C, magnetic hyperthermia,
X-ray, enzymes…)
Polymer Self‐assembly and Life Sciences
Highlights
‐ First multi‐functional polymersomes for theranostics
with targeting
Advanced Materials 17, 712 (2005)
J. Mag. Mag. Mat. 300, 71 (2006)
ACS Nano 5, 1122 (2011)
Soft Matter 7, 9744 (2011)
J. Contr. Rel. 169, 165 (2013)
Adv. Health. Mater. 2, 1420 (2013)
Chem. Soc. Rev. 42, 7099 (2013)
Magnetic polymersomes
‐ Concept of “self‐targeting polymersomes” with biomimetic simplified glycoprotein analogues
“glycopeptosomes”
Angew. Chem. 48, 2572 (2009)
Biomacromol. 10, 2802 (2009)
Biomaterials 31, 3882 (2010)
Macromol. Biosc. 10, 503 (2010)
Nanomedicine 8, 71 (2012)
J. Am. Chem. Soc., 134,119 (2012)
Chem. Commun. 48, 8353 (2012)
J. Am. Chem. Soc. 134,20189 (2012)
Biomacromolecules 14, 2973 (2013)
Faraday Discus. 166, 137 (2013)
Chem. Comm. 50, 3350 (2014) Polymer Self‐assembly and Life Sciences
Highlights
‐ Compartmentalized polymersomes: towards “plastic cells”
Langmuir 27, 9034 (2011)
Angew. Chem. 51, 1173 (2012
Langmuir 28, 2035 (2012)
Chem. Soc. Rev. 42, 512 (2013)
Angew. Chem. (2014, 53, 146)
Compartmentalized polymersomes
‐ Deep understanding of polymer membrane properties and hybrid lipopolymersomes
PDMS-g-PEO/DPPC
Eur. Phys. J. E, 34, 14 (2011)
Soft Matter 8, 2867 (2012)
Materials Today 16, 397 (2013)
ACS Nano 7, 9298 (2013)
25µm
Membrane properties modulation
Multifunctional polymersomes for drug delivery
Objectives: Design amphiphilic and biofunctional copolymers for therapeutic and imaging purposes
Multi‐functional polymersomes for theranostics
1000
S
(q)
intra
R =45nm (PDI=0.35) =9nm
H
100
-2
S
intra
(q)
q
10
1
-4
q
0.1
0.01
0.001
0.01
0.1
1
-1
q (Angstrom )
Cell internalization by FACS and confocal analysis
Breast cancer cell lines:
FITC posi ve cells (%)
90
MDA MB 231
Confocal analysis (BT474)
BT474
80
70
60
50
Overexpress HER2
(Human Epidermal Growth
Factor Receptor-2)
40
30
20
10
0
Negative
Cellscontrol
(buffer)
Naked
Cells
+ NP
particles
37°C
Anti
mAbCellsHER2
+ NP‐Her
grafted particles
37°C
Anti+NP‐Her
HER2 mAbCells
4°c
grafted particles
4°C
FITC-NPs
Advanced Materials 17, 712 (2005); J. Mag. Mag. Mat. 300, 71 (2006); J. Control. Rel. 147, 428 (2010); ACS Nano 5, 1122 (2011); Soft Matter 7, 9744 (2011); J. Contr. Rel. 169, 165 (2013); Chem. Soc. Rev. 42, 7099 (2013); Adv. Health. Mater. 2, 1420 (2013)
FITC-NPS+ HER
« Intelligent » polymers: code the structural and biofunctional information in the polymer chain structure
Angewandte chemie 51, 3060‐3062 (2012)
Strategies towards bioactive polymer‐based nanovehicles: from synthetic block copolymers to biosynthetic protein polymers
E. Garanger (LCPO), Col. A. Chilkotti, S. Mac Ewan, Duke (USA)
Synthetic virus from glycoproteins mimick self‐assembly
“Glycopeptosomes” are mimicking both the structure and function of viral capsids
3D‐representation of glycoproteins at the surface of dengue virus
Schatz et al. Macromol. Rapid Comm. 19, 1664‐1684 (2010)
Bonduelle et al. Biomacromolecules 14, 2973‐2983 (2013)
Synthetic glycopolypeptides and bio‐active nanopaticles
Bonduelle et al. J. Am. Chem. Soc. 134,20189 (2012)
Faraday Discus. 166, 137 (2013); Biomacromolecules 14, 2973 (2013)
Design of a « plastic cell »
M. Marguet et al. Angew. Chem. 53, 146 (2014) highlight in Nature Chemistry 2014
Acknowledgements (people and funding) http://www.lcpo.fr
Group members:
E. Garanger, E. Ibarboure,
J.-F. Le Meins, S. Lecommandoux
C. Schatz, O. Sandre
PhDs
C. Legros
V. Ibrahimova
M. Asano
H. Duan
R. PetitDemange
T. T.P. Dao
A. V-T. Nguyen
Postdocs
A. Lu
C. Gauche
(S. Zhang)
(K. Ferji)
Master students: A. Peyret, L.
Rodrigues, G. Hemery, P. Lefrançois
The « IUPAC Team »: T. Deming, A. Heise, H. Schlaad, H. Menzel
Recent Alumini
C. Drappier, L. Bataille, J. Thévenot, M.
Marguet, H. Oliveira, L. Bui, S. Louguet, A.
Carlsen, A. Kumar, C. Sanson, K. Upadhyay,
A. Perro, W. Agut, D. Bacinello, C. Bonduelle,
S. Mazzaferro, R. Salva, K. Zimny, T. Paira
The ESF-RNP : Precision Polymer Materials (P2M)
Participation to international networks and projects
Long term experience in working with industrial partners:
L’Oréal, Firmenich, Adocia, Debiopharm, Servier, Guerbet, Pharmamar, …
In addition to our participation to ACS, MRS, SFC, GFP, GTRV (SFNano) and our involvement in international (IUPAC, Europe, Euskadi) and national Grants (ANR, CNRS, CRAquitaine), we built strong international links and are/were involved in:
“Bimodal PET‐MRI molecular imaging technologies and applications for in vivo monitoring of disease and biological processes”
Coordinator: G. Loudos, TEIA, Greece
For France: D. Viskikis, VISVIKIS, INSERM U650, LaTIM
S. Lecommandoux, O. Sandre, LCPO, CNRS U‐Bordeaux
Coordinator: J.P. Aimé, U Bordeaux, France
“Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (RADIOMAG) Coordinator: S. Spassov, meteo, Belgium
”
"Core group" of management comitee: C. Billotey (Lyon, France), S. Bégin (IPCMS, Strasbourg),
O. Sandre (LCPO), D. Ortega (IMDEA nanoscience, Madrid), S. Dutz (U. Ilmenau, Germany)
“Precision Polymer Materials”
Coordinator: S. Lecommandoux, U Bordeaux, France
Synthesis and properties of glycopolypeptide biohybrid materials Theme: Novel Polymer Synthesis Coordinator: Tim Deming, UCLA, USA
Integration of novel nanoparticle based technology for therapeutics and diagnosis of different types of cancer
 We look for partners to build a consortium on image‐guided nano‐
therapies where we can offer leading a WG on realistic polymer nanomedicine
IUPAC
LCPO, Université de Bordeaux
Laboratoire de Chimie des Polymères Organiques,
CNRS - ENSCBP – University of Bordeaux
Pessac, France www.lcpo.fr
[email protected], [email protected]