Endomagnetics: healthcare by sensing, moving and heating magnetic nanoparticles in the human body. Quentin Pankhurst

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1 Endomagnetics: healthcare by sensing, moving and heating magnetic nanoparticles in the human body Quentin Pankhurst Deputy Director London Centre for Nanotechnology

2 Outline Magnetic therapy through the ages from Mesmer to MRI Imaging, actuating, heating a selection Prospects and challenges

3 Magnetic therapy through the ages Franz Anton Mesmer

4 Magnetic therapy through the ages Dr Graham s Temple and the Celestial Bed 1781 Emma Lyons (Lady Hamilton)

5 Magnetic therapy through the ages The Dr. Philpott Designed and Approved Polar Power Super Bed Grid

6 Magnetic therapy through the ages The serious stuff: magnetic resonance imaging (MRI)

7 Magnetic therapy through the ages The serious stuff: magnetic resonance imaging (MRI)

8 Magnetic therapy through the ages The serious stuff: magnetic resonance imaging (MRI)

9 Why magnetic nanoparticles are useful Their size is smaller than or comparable to a cell ( µm) a virus ( nm) a protein (5-50 nm) a gene (2 nm wide and nm long) They can be actuated by a magnetic field gradient action at a distance They can resonantly respond to a time-varying field energy transfer

10 Nanomagnets for Healthcare SENSING MOVING HEATING

11 Staging and Treating Breast Cancer Lymph node surgery: painful or pot-luck Surgeon operates to remove tumour but has the cancer spread? If it has, the first metastases form in lymph nodes in the armpit Endomagnetics: keyhole surgery Ignoring the spread: untreated recurrence in 10% of cases Decades-long practice, still followed in 85% of cases, is to ignore spread, or remove all the nodes in the armpit Removing all the nodes: radical surgery, impairs quality of life

13 Prototype: SQUID Processor Design brief: to be able to detect 100 µg of magnetic dye 30 mm from the probe s tip.

14 Prototype: longitudinal Design target met: detect 60 pt lateral (end on sample)

15 Clinical trials: University College London Hospital: started 20Dec06.

16 Clinical trials:

18 Nanomagnets for Healthcare SENSING MOVING HEATING

19 Moving: Targeted drug delivery

20 Forces on a magnetic nanoparticle: F m = (m ) B F m = V m χ (½ B H) Hydrodynamic drag force: Equating the two: F d = 6 π η R m v

21 Stem Cell Treatment of Atherosclerosis So few get where they re needed Stem cells are produced by the body as a universal type of cell that can replace tissues when they are damaged or worn out Endomagnetics: actuation They are few in number and hard to get They are found in small numbers in tissues, such as bone marrow They do not home to the area of damage

fluorescent-conjugated Bangs particles DAB-enhanced

22 Stem Cell Treatment of Atherosclerosis In vitro labelling of Ntera2 stem cells with red fluorescent-conjugated Bangs particles DAB-enhanced Prussian blue staining for iron following in vitro labelling with Endorem

23 MAGNET MAGNET MAGNET MAGNET Timelapse actuation of Endorem labelled CD133 cells

24 Prototype: 250 ml water with 5.6 mg/ml Endorem pumped at 60 ml/h for 3 h in the presence of a permanent magnet

25 Prototype: We see significant magnetic capture:

26 Prototype: Halbach array: At 2 mm: db/dz = 66 T m -1

27 Nanomagnets for Healthcare SENSING MOVING HEATING

28 Heating: Microwave oven Magnetic field hyperthermia

29 Heating: Magnetic hyperthermia M P = f H dm µ FMP o P SPP = µ o π f χ" H 2 H

30 Heating: Promising results from animal trials Sirtex Ltd.

31 Sledgehammernut, but where is the nut? Treatment of Metastatic Cancers Virtually all cancers can spread by local extension, through the bloodstream, or through the lymphatic system Endomagnetics: antibody vector, heat locally Treatment by chemotherapy and radiotherapy Metastases can be hard to see before they are a few mm in size Systemic, so healthy cells and tissues also suffer

32 Prototype: Magnetic field Fab Fv antibody-np scfv Cancer cell Fc Antibody NP HEAT

33 Prototype: We have made conjugates: H --N=C--- ~20nm

34 Prototype: Covalent linkage of MFE-23 to oxidised dextran MNP: C OH Oxidised with sodium periodate C O NH 2 Sodium borohydride COOH C =N Molday et al, 1982 H COOH

35 Prototype: Human cell & clinical: LS174T cells (blue) with MFE targeted nanoparticles (red) MFE localised in liver tumour

36 Prototype: Particle synthesis and heating:

37 Prototype: We see both conjugation and heating: OD Value 490nm Antibody Antibody-Nanoparticle Nanoparticle Temperature rise (C) Chemicell 7 mg/ml NP1 7mg/ml NP2 3mg/ml Time (s).. and our work is continuing.

38 Summary Magnets can be used to deliver forces and energy, and can be sensed remotely Magnetic nanoparticles can be used both in vivo and in vitro, to great effect Endomagnetics has real promise for oncology, hematology, drug delivery, stem cell therapies

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