Barbara La Ferla Marzia Lecchi Francesco Nicotra Davide Prosperi Paolo Tortora Ivan Zanoni Cristina Airoldi Andrea Becchetti Laura Cipolla Miriam Colombo Rita Grandori Francesca Granucci Nanobiotecnologie in BTBS IMPLEMENTATION STRATEGIES: -rationalize fund raising and technology transfer strategies -favor interactions/ collaborations with enterprises -favor interactions /collaborations among BTBS groups -support external collaborations -share and implement common instruments and facilities EGO
Transcript
Barbara La FerlaMarzia LecchiFrancesco NicotraDavide ProsperiPaolo TortoraIvan Zanoni
Cristina Airoldi Andrea Becchetti Laura Cipolla Miriam ColomboRita GrandoriFrancesca Granucci
Nanobiotecnologiein BTBS
IMPLEMENTATION STRATEGIES:-rationalize fund raising and technology transfer strategies-favor interactions/ collaborations with enterprises-favor interactions /collaborations among BTBS groups -support external collaborations-share and implement common instruments and facilities
EGO
Nanobiotechnology
“There’s plenty of room at the bottom”RichardFeynmann
1965 Nobel Prize in Phisics
Trend of Total Global Nanotechnology Funding (US $ Billion)
Menaa, J Bus Fin Aff 2014, 3:1
Nanobiotechnology
Monitoring, repair, construction and control of human biological systems at the molecularlevel, using engineered nanodevices and nanostructures
Targeted Superparamagnetic Iron Oxide NPsTargeted Perfluorocarbon particles
Targeted Quantun Dots for diagnosisDendrimer based contrast agents
Multy-functional drugd with imaging labels
Molecular Nanopore DevicesBio-Engineered Viruses and Bacteria
Artificial Microbes for DNA standsLow Friction Carbon Nanotube BearingDNA-Based synthetic polyeders and manipulatorsNano-Tweezers based on Carbon Nanotubes
Biomolecular motors
Tissue regeneration with polymeric scaffolds
Bio-Engineered Tissues and Extra Cellular matrixAtomic and Molecular Switches and Memories
Bio-Compatible Polymer Electric CircuitsCOMPLEXITY
The stages of discovery ……… and the perspectives
M.L. Etheridge et al / Nanomedicine: Nanotechnology, Biology, and Medicine 9 (2013) 1–14
M.L. Etheridge et al / Nanomedicine: Nanotechnology, Biology, and Medicine 9 (2013) 1–14
Areas of use
0102030405060708090
1 2 3 4 5 6 7 8 9
Series2Series1
TherapeuticsInvestigationalCommercial
Numb
erof
appli
cation
s/prod
ucts
0
5
10
15
20
25
30
1 2 3 4 5 6 7 8 9 10 11
Series2Series1
DevicesInvestigationalCommercial
Numb
erof
appli
cation
s/prod
ucts
Nanoparticles
Drug deliveryDiagnostics
Nanostructured materials
Regenerative medicineDevices for slow release of drugs
Nanoparticles for Drug Delivery Drugs must be administered in large quantities in order to allow only for a small amount to reach the biological target
A coach to safely transport the drug
0
10
20
30
40
50
60
70
80
90
1 2 3 4 5 6 7 8
Series2Series1
InvestigationalCommercial
Numb
erof
appli
cation
s/prod
ucts
Dimension in nmM.L. Etheridge et al / Nanomedicine: Nanotechnology, Biology, and Medicine 9 (2013) 1–14
Dimensions
FDA approval Trade name nanomaterial drug indications 1995 Doxyl®, Cealix®
(Johnson & Johnson)PEG-liposomes doxorubicin Metastatic ovarian or breast
cancer;AIDS-related Kaposi’s sarcoma
1995 Abelcet®(Enzon/ Sigma-Tau)
Liposomes/lipid NPs
Amphotericin B Invasive fungal infections
1996 DaunoXome®(Galen)
Liposomes/lipid NPs
doxorubicin HIV-related Kaposi’ssarcoma
1997 AmBisome®(Gilead)
Liposomes Amphotericin B Fungal infections
1999 DepoCyte®(Sigma Tau)
Liposomes/lipid NPs
Cytarabine Limphomatous meningitis
2000 (in EU and Canada)
Myocet®(Cephalon)
Liposomes/lipid NPs
doxorubicin metastatic breast cancer
2001 (Taiwan) Lipodox®(Taiwan Liposomes)
PEG-liposomes doxorubicin Karposi’s sarcoma, breast and ovarian cancer
2002 Pegintron®(Shering Plough)
Polymer protein conjugate
Peginterferon alpha-2b
Chronic hepatitis C
2003 Estrasorb®(Graceway)
Micelles Estradiol Menopausa
2004 DepoDur®(Pacira Pharm.)
Liposome Morphine Analgesic
2004 Macugen® (OSI Pharma)
PEG-polymer-aptamer conjugate
siRNA anti-VEGF Age-related macular degradation
2005 Abraxane®(Abraxis BioScience)
Albumin NPs paclitaxel Various cancers
2012 Marqibo®(Talon)
PEG-liposomes Vincristine Leukemias, lymphomas, and other hematologic cancers
Some Relevant Clinically Approved NPs (nanocristals not included)
5mg/5ml kits (Qty:1)appx. price $11.022
The journey of NPs into the body
Administration mode
M.L. Etheridge et al / Nanomedicine: Nanotechnology, Biology, and Medicine 9 (2013) 1–14
Active Targeting: receptor mediated endocytosisDelivery machanisms : endocytosis, disruption of the endocytes and release of the drug (pH, GSH, light…)
The biological barriers
Nanobiotechnologies for preclinical studies
Biomolecularmechanisms of pathologies and
aging
Early diseasediagnosis
Drug delivery and targeting
METHODS AND TECHNOLOGIES: synthetic nanotechnology,morphostructural characterization of nanosystems, cellular and mouse models, supramolecular (bio)chemistry, synthetic and medicinal chemistry, bioinformatics, native mass spectrometry, biophysics, NMR molecular interaction studies, functional studies,ultrastructural analysis of biological samples.
New nanostructured
biomaterials
TUMOR DIAGNOSTICS Development of novel colloidal andbiomimetic nanoparticles (NPs) consisting of1) a magnetic core, useful as MRI contrast agent, and anorganic shell responsible for cell receptor targeting action:- NPs synthesis, characterization and functionalization withbiomolecules- In vitro studies in cells (viability, interactions, signaling)- In vivo studies on tumor bearing mice2) Engineered nanocages deriving from natural sources for theselective delivery of therapeutic agents at the tumor site
TUMOR TARGETING. Drug-loaded nanoparticles can be usedto target selective cancer cells resulting in the localization ofthe therapeutic activity, which should strongly reduce the typicalside-effects usually encountered with conventionalchemotherapeutics.
DIAGNOSIS AND THERAPY WITH NANOPARTICLES (THERAGNOSTICS)
ANTIVIRAL THERAPEUTICS. Nanotechnology has potential inHIV treatment by two approaches1) improving the pharmacodynamic and pharmacokineticproperties of antiretroviral drugs2) assisting drugs in crossing the biological barriers (e.g., theblood brain barrier) to target the virus reservoirs.
INFLAMMATORY DISEASES. Bioengineered nanoparticles canbe developed to localize, monitor and quantify the earlystages of inflammatory bowel diseases (IBDs), particularlyCrohn disease and ulcerative colitis, and to treat aggressiveinflammatory disorders including IBDs, rheumatoid arthritis,transplant rejection, edema, sepsis, and other inflammatoryconditions.
INNOVATIVE WAYS TO DELIVER NPS ALTERNATIVE TOTHE TRADITIONAL INTRAVENOUS ROUTES OFADMINISTRATION In vivo investigation of topical, oral andintranasal administration as promising non-invasive deliveryoptions especially for a regional and/or local effect,ameliorating the patient compliance, improving thepharmacokinetics of degradable peptides and proteins, andreducing the frequently occurring side-effects of therapies.
COSMETIC APPLICATION Synthesis andapplication of Silver and TiO2 NPs asalternative antibacterial agents to toxicparabens in cosmetics
SUSPENSION
Controlstreated mice
CREAMSUSPENSION
www.nanobiolab.btbs.unimib.it Miriam Colombo
Anti Inflamatory NPs
Francesca GranucciIvan ZanoniDavide Prosperi
Phagocytosis of NPs has been exploitedto inhibit inflamation targeting NFAT pathway
N
S - S
N
S-S N
N
S-S
N
S-S
N
NANOPARTICLES
MYTS
MYTS-VIVIT
PEGVIVIT
Patent n°: PCT/IB2013/055943
Fe3O4
NPstreatment
STOP TREATMENT
NPs treatment reduces allograft rejection
DAY 50
0
20
40
60
80
100
120
DAY 0 DAY 15 DAY 35 DAY 50 DAY 70
% SUCCESS
M in MM in FM in F+NPs-VIVITM in F+FK506
STOP TREATMENT
Francesca GranucciIvan Zanoni
SKIN TRANSPLANT MODEL –mH-Ag mismatched
Sterile inflammationACUTE TRANSPLANT
REJECTION
Awarded as Best Completed Projects launched under the EU Framework Programmes
Nanoparticles for therapy and diagnosis of Alzheimer’s Disease
http://bioorgunimib.com/btbs/
Massimo Masserini, coordinatorFrancesco NicotraBarbara La FerlaCristina Airoldi
N N
HO OH
NN
N (PEG)
NH
O
O O
N
O
OS
(PEG)
liposome
GRKKRRQRRRPPQGWC
Uptake of Curc-NL and TAT-Curc-NL by hCMEC/D3 cellmonolayers by radiochemical technique. 6×104 cells were incubated with NL labelled with [3H]-Sm for 3 h at 37°C, 5% CO2. After incubation, the uptake of Curc-NL or TATCurc-NL by hCMEC/D3 cells has been assessed by following both tracers used, [3H]-Sm (grey bars) by radioactivity counting, and Curc-PEG-lipid (black bars) by mass spectrometry.
http://bioorgunimib.com/btbs/Barbara La FerlaGiulio Sancini
Cellulose nanocrystals (CNCs) for bone tumor targeting
liver spleen
OPTIC SCAN
Barbara La FerlaMarco Orlandi, Luca ZoiaMario Salmona, Paolo Bigini MARIO NEGRI INSTITUTE
� Define and develop better tools for Structural Biology and Structural Proteomics
� Structure and function of dynamic and heterogeneous systems which are otherwise difficult to study and are prime targets for drug development (Parkinson's and Alzheimer's)
� Investigating interactions of proteins with membranes and nanoparticles for development of novel biosensors and drug-delivery tools
Coordinator: Frank Sobott (Antwerp)
MC members Italy: Rita Grandori Andrea Urbani (Rome Tor Vergata)
Smart Nanostructured Biomaterials for Regenerative Medicine
http://bioorgunimib.com/btbs/
Innovative chemical methodologies for smart biomaterials
Francesco Nicotra, coordinatorLaura Cipolla
Walking Track Analysis (WTA) at 24 days post implantation
Osteoarthritic models in mice treated with glycosylated-collagen
show different cartilage repair depending on the nature of the sugar
