FP7-ICT-2007-2 Nano-Actuators and Nano-sensOrs for ...NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications (2) NANOMA PartnersNANOMA Partners • Partner 1 University of

(1)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications

1

FP7-ICT-2007-2

Nano-Actuators and Nano-sensOrs for Medical Applications

NANOMA

FP7-ICT-2007-2

Nano-Actuators and Nano-sensOrs for Medical Applications

NANOMA

Coordinator: Antoine FERREIRA

Université d’Orlé[email protected]


NANOMA PartnersNANOMA Partners

• Partner 1 University of Orléans (Coord.) (UORL) - France• Partner 2 Zenon S.A. (Zenon) - Greece

• Partner 3 ETH Zurich (ETHZ) - Switzerland

• Partner 4 Universität Oldenburg (Amir) - Germany

• Partner 5 Biomedical Research Foundation (BRF) - Greece

• Partner 6 University of Cyprus (UCY) - Cyprus

• Partner 7 FemtoTools (FemtoTools) - Switzerland

• Partner 8 Hospital Oldenburg (HOld) - Germany


NanoRobotics – Ultra-Local Drug DeliveryNanoRobotics – Ultra-Local Drug Delivery

(Opensource Handbook of Nanoscience and Nanotechnology)

Challenge 1

Challenge 2

Challenge 3

Improved imaging

Localized therapy

Killing the cancer cells

Molecular Imaging & Therapy


Present State-of-the-Art in Magnetic Targeting (Trapping)

Present State-of-the-Art in Magnetic Targeting (Trapping)

• Magnet is positioned to trap the magnetic particles in order to deliver therapeutic agents;

• No navigation hence particles must be delivered close to the target but still loosing a significant quantity of particles;

• Only for targets near the skin due to higher gradient field towards the magnet;

• No closed-loop control since the particles cannot be tracked (lack of imaging modality).

Magnetic Field

Body surface


Early cancer stage I

Microcaprule-based drug delivey

Magnetic microcapsule sterring using MRI ystem

NANOMA ConceptNANOMA Concept

1. Enhanced diagnostics using MRI,

2. In-Vivo propulsion and navigation,

3. Targeted drug delivery using functionalized nanovectors.

New approach for diagnosing and New approach for diagnosing and treating breast cancer :treating breast cancer :

Concept and Motivation: Concept and Motivation: NANOMA aims at developing drug delivery microrobotic systems (composed of nanoActuators and nanoSensors) for the propulsion and navigation of ferromagnetic microcapsules in the cardiovascular system through the induction on magnetic gradients.


NANOMA ObjectivesNANOMA Objectives

Scientific and Technological Objectives: Scientific and Technological Objectives:

•• Design and modeling of nanorobotic capsules: Design and modeling of nanorobotic capsules: Energy approach based on multi-scaled and multi-physics modeling and interactive computational tools.

•• FunctionalizationFunctionalization--based targeting of biocarriersbased targeting of biocarriers : : Biodistribution-driven mechanisms using surface functionalization processes at the nanocapsule surface (f-CNT and f-NP).

•• MRI navigable biocarriers in blood vessels : MRI navigable biocarriers in blood vessels : The integration of ferromagnetic particles allows potential MR-tracking and automatic delivery of biocarriers through induced forces generated by magnetic gradients from an upgraded MRI system.

• InIn--vivo MRvivo MR--tracking drug delivery in mouse cancer models: tracking drug delivery in mouse cancer models: Efficiency of drug release at specific site (breast cancer cell and/or tumor) will be tested (proof-of-concept): Cell lines and In-vivo,


Multidisciplinary FieldMultidisciplinary Field

Beneficiaries: BRF, HOld

Beneficiaries: ETHZ, UCY, Amir, FemtoTools

Beneficiaries: ZENON, UORL


Virtual Environment

Biomotors

Structures

Bonding

Links

Virtual manipulation

DatabaseX-ray or NMR Molecular

docking

• carbon-carbon

• DNA-carbon

• biotin-avidin

• H-bonds

Connecting

•Multi-finger haptic rendering

• 3D visual rendering

Force feedback

Multiscale Models

Interactive Modeling

SimulationDataglove

3D Vision

VR Interfaces

• Steering forces• Temperature and pH variation

Haptics

Design MethodologyDesign Methodology


3D Computer-Aided Design3D Computer-Aided Design

(a) PEG‐functionalized polymer nanoparticle , (b) PEG‐functionalized carbon nanotube with encapsulated magnetic material, (c) encapsulated drug delivery for drug release.


29/06/200910

Example of Design and SimulationExample of Design and Simulation

Nanocapsule design

Peptides

Drug Encapsulation

Lipid bilayer was Lipid bilayer was composed of 256 CG composed of 256 CG

DMPC lipids DMPC lipids

• Doxorubicin

• Epirubicin

• Taxol,

• Cytoxan.


FexOyFexOy

water

Fe3+/Fe2+Fe3+/Fe2+

NH4OHFe2+/Fe3+

1) Magnetic Functionalization, Stabilization and Targeting of Polymer-based Micellar Nanoparticles

2) Functionalization of Nanotube Capsules

(a) CNTs filled with Magnetic Nanowires

(b) Filling iron oxide/nickel nanoparticles into CNTs

(c) Decorating iron oxide/nickel nanoparticles onto CNTs

Magnetic Functionalization of NanocapsulesMagnetic Functionalization of Nanocapsules

Magnetic nanoparticles will be used for MRI magnetic field actuation / guiding / tracking of the CNT capsules.


• Objectives• Shell engineering processes

for fabricating CNT capsules will be implemented. The functionalization (filling and decoration) of CNTs with magnetic particles, bio active peptides, and polymers will also be investigated.

As-grown CNTs

Electric BreakdownMechanical Destruction Ultrasonic/Acid-etching

Mechanical Destruction

Electric Breakdown


Baking after washing


Ultrasonic/Acid-etching

Ultrasonic/Acid-etching

Magnetic Functionalization of NanocapsulesMagnetic Functionalization of Nanocapsules


Biological Functionalization of NanocapsuleBiological Functionalization of Nanocapsule

• Description of Tasks:

1.Magnetic and bio-chemical nano-functionalization with linked colloidal magnetite nanoparticles and antibodies.2.Thermal-mechanical nano-functionalization with nanoheater linked rods and bilayers.

• Objectives:- Bio-chemical surface functionalization of nanocapsule for target recognition and binding.- Structure characterization of components and

testing of their actuation properties in magnetic steering.


MRI-Based Tracking and Propulsion of CapsulesMRI-Based Tracking and Propulsion of Capsules

• Can implement the three essential components for real-time controlled navigation of untethered devices in the human vasculature:

– Propulsion• Using the three imaging

orthogonal coils of the MRI system and implementing additional software

– Tracking• Using the conventional hardware

and software of the MRI system

– Control• By implementing control

algorithms on the computer system of the MRI platform based on tracking information


Fundamental Theory of Magnetic Propulsion using MRI

Fundamental Theory of Magnetic Propulsion using MRI

Magnetic Resonance Propulsion (MRP)

Schematic of the clinical MRI and its typical configuration

The induced force (F) depends on the volume (V) of the ferromagnetic core, the magnetization saturation (M) of the material, the magnetic gradients applied with 3D directional control from the three orthogonal coils.

• Magnetic force scales down L3 while drag force decreases L at low Re

• Gradient coils in the MRI bore are limited,

• Hard to track if not sufficient number of particles together;

•Small blood vessels cannot imaged.


Timeline for tracking and propulsion used within the environment of the MRI platform for the closed-loop displacement along pre-planned paths in blood vessels.

Timeline for Tracking and PropulsionTimeline for Tracking and Propulsion

Martel et al. (2006), Applied Physics Let.


Tracking and NavigationTracking and Navigation

b c d

MRI diagnostics of breast cancer

Magnetic steering navigation ? Path planning of nanocapsules

Magnetic and Biologically functionalized CNT

a


Demonstration ScenariiDemonstration Scenarii

• Recognition and Tracking of an Object• Propulsion along a preplanned path• No flow, no overly complicated structure

PHASE 1: HumanPHASE 1: Human--sized Phantomsized Phantom

PHASE 2: AnimalPHASE 2: Animal

The efficacy and cytotoxicity studies will be performed initially in cells in culture.

PHASE 3: Cell CulturePHASE 3: Cell Culture

• Injection• Tracking• Propulsion/Control

(19)NANOMA: Nano-Actuators and Nano-Sensors for Medical ApplicationsContactsContacts

Co-ordinator : Prof. Antoine FERREIRAUniversity of OrléansInstitut PRISME

Email: [email protected]

http://nanoma.zenon.gr/

Documents

FP7-ICT-2007-2 Nano-Actuators and Nano-sensOrs for ...NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications (2) NANOMA PartnersNANOMA Partners • Partner 1 University of