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Electronic Supplementary Information

Nano-thermometer with Thermo-sensitive Polymer Grafted USPIOs behaving as Positive Contrast Agents in low-field MRI Adeline Hannecart,a Dimitri Stanicki,a Luce Vander Elst,a,b Robert N. Muller,a,b Sébastien Lecommandoux,c Julie Thévenot,c Colin Bonduelle,c Aurélien Trotier,d Philippe Massot,d Sylvain Miraux,d Olivier Sandre,*c and Sophie Laurent,*a,b

aDepartment of General, Organic and Biomedical Chemistry, NMR and Molecular imaging Laboratory, University of Mons, 19 avenue Maistriau B-7000 Mons, Belgium. Fax: +32-65-373520; Tel: +32-65-373525; E-mail: sophie.laurent@umons.ac.be b Center for Microscopy and Molecular Imaging, 8 rue Adrienne Bolland, B-6041 Charleroi, Belgium c Laboratoire de Chimie des Polymères Organiques, UMR5629 CNRS / Université de Bordeaux, ENSCBP 16 avenue Pey Berland F-33607 Pessac, France. Fax: +33-5-4000-8487; Tel: +33-5-4000-3695; E-mail: olivier.sandre@enscbp.fr d Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS / Université de Bordeaux 146, rue Léo Saignat, F-33076, Bordeaux France a)

b)

Fig. S1 a) 500 MHz 1H NMR spectra of Jeffamine® M-2005 in D2O (30 mg/ml) at increasing temperatures (10, 15, 20, 25, 30, and 35°C); b) 500 MHz 1H NMR spectra of Jeffamine® M-2070 in D2O (30 mg/ml) at increasing temperatures (35, 40, 50, 60, 65, 70, 75, 80, and 85°C).

10°C

15°C

20°C 25°C 30°C 35°C

35°C

40°C

50°C

60°C

65°C

70°C

75°C

85°C

80°C

Electronic Supplementary Material (ESI) for Nanoscale.This journal is © The Royal Society of Chemistry 2015

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a)

b)

Fig. S2 FT-IR spectra of iron oxide nanoparticles obtained by coprecipitation (a) and of iron oxide nanoparticles coated with TEPSA (b).

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a)

b)

Fig. S3 Thermogravimetric analyses (TGA) of USPIOs silanized by TEPSA (red curve), and after coupling with Jeffamine® M-2005 (green curve) and Jeffamine® M-2070 (blue curve). The graphs are normalized either by the dry weight after the plateau at 120°C (a) or by the burnt weight after the treatment at 600°C under air (b), enabling to subtract the silane content from the total organics to get the polymer weight % relatively to iron oxide, see Equation (4) in the text.

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a)

b)

Fig. S4 a) Difference between the normalized FT-IR spectra of USPIOs coated with TEPSA before and after grafting of Jeffamine® M-2005, b) and spectrum of Jeffamine® M-2005 alone.

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a)

b)

Fig. S5 a) Difference between the normalized FT-IR spectra of USPIOs coated with TEPSA before and after grafting of Jeffamine® M-2070, b) and spectrum of Jeffamine® M-2070 alone.

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a) b)

Fig. S6 NMRD profiles of the longitudinal relaxivity vs. proton Larmor frequency for a) TEPSA-coated USPIOs, and b) USPIOs grafted with Jeffamine® M-2070 as a function of temperature.

a) b)

Fig. S7 a) Outer Sphere radius RNMR (nm) and b) saturation magnetization Ms (A∙m2∙kg-1) vs. temperature deduced by fitting the NMRD profiles for USPIOs coated by Jeffamine® M-2070 (green markers) and TEPSA only (purple markers).

Proton Larmor Frequency (MHz)0.01 0.1 1 10 100

r 1 (s

-1m

M-1

)

0

10

20

30

40

50

Proton Larmor Frequency (MHz)0.01 0.1 1 10 100

r 1 (s

-1m

M-1

)

0

10

20

30

40

50

25°C37°C45°C50°C

Temperature (°C)20 25 30 35 40 45 50 55

Out

er S

pher

e ra

dius

RN

MR

(nm

)

4.0

4.5

5.0

5.5

6.0

Temperature (°C)20 25 30 35 40 45 50 55

Mag

netiz

atio

n M

S (A

m²/K

g)

40

45

50

55

60

NP-TEPSANP-TEPSA-Jeffamine M-2070

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a) b)

c) d)

e) f)

g) h)

Fig. S8 Longitudinal r1 (a, c, e, g) and transverse r2 (b, d, f, h) relaxivities of USPIOs grafted with Jeffamine® M-2005, normalized by the corresponding r1 or r2 of TEPSA-coated USPIOs, as functions of temperature from 10 to 50°C, for clinically relevant frequencies: 8.25 MHz (a, b), 20 MHz (c, d), 60 MHz (e, f), and 300 MHz (g, h). The vertical dotted lines show the position of the LCST of Jeffamine® M-2005, concomitant with an inflection of the curves of both the r1 and r2 relaxivities vs. temperature.

Temperature (°C)10 20 30 40 50 60r 2

(NP-

Jeffa

min

eM20

05)/

r 2 (N

P) 8

.25

MH

z

1,1

1,2

1,3

1,4

1,5

1,6

1,7

1,8

1,9

Temperature (°C)0 10 20 30 40 50r 1

(NP

-Jef

fam

ineM

2005

)/ r 1

(NP

) 20

MH

z

0,4

0,5

0,6

0,7

0,8

0,9

Temperature (°C) 0 10 20 30 40 50r 2

(NP

-Jef

fam

ineM

2005

)/ r 2

(NP

) 20

MH

z0,75

0,80

0,85

0,90

0,95

1,00

1,05

Temperature (°C)

0 10 20 30 40 50 60r 1 (N

P-Je

ffam

ineM

2005

) / r 1

(NP)

60

MH

z

0,40

0,45

0,50

0,55

0,60

0,65

0,70

0,75

0,80

Temperature (°C)0 10 20 30 40 50 60r 2

(NP-

Jeffa

min

eM20

05)/

r 2 (N

P) 6

0 M

Hz

0,75

0,80

0,85

0,90

0,95

1,00

1,05

Temperature (°C)24 26 28 30 32 34 36 38 40 42r 1

(NP

-Jef

fam

ineM

2005

)/r1

(NP

) 300

MH

z

0,20

0,25

0,30

0,35

0,40

0,45

0,50

0,55

0,60

Temperature (°C)24 26 28 30 32 34 36 38 40 42r 2

(NP-

Jeffa

min

eM20

05)/r

2 (N

P) 3

00 M

Hz

1,6

1,8

2,0

2,2

2,4

2,6

2,8

3,0

Temperature (°C)

0 10 20 30 40 50 60r 1 (N

P-Je

ffam

ineM

2005

)/ r 1

(NP)

8.2

5 M

Hz

0,55

0,60

0,65

0,70

0,75

0,80

0,85

0,90

0,95