Exploring the structure-property relationships of ultrasonic/MRI dual imaging magnetite/PLA microbubbles: magnetite@Cavity vsrsus magnetite@Shell systems

Bin Xu#1, Rong Lu#1, Hongjing Dou*1, Ke Tao1, Kang Sun*1,Yuanyuan Qiu2, Jing Ding3, Dong Zhang2, Jiyu Li3, Weibin Shi3, and Kun Sun3

1State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering,Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China

2Institute of Acoustics, Nanjing University, Nanjing 210093, China

3Department of General Surgery , Xinhua Hospital ,School of Medicine , Shanghai Jiao Tong University , Shanghai, 200092,P. R. China

*Corresponding author. E-mail: , .

#These authors contributed equally to this work.

SUPPORTING INFORMATION

The XRD pattern of magnetite nanoparticles (Fig. S1a) confirms the containing of Fe3O4 nanocrystals because the position and relative intensity of the main peaks match well with those from the JCPDS card (19-0629) for Fe3O4.

Fig.S1XRD pattern (a) and TEM image (b) of magnetite nanoparticles embedded in Fe4O4 @ Shell composite microbubbles.

Fig. S2TEM image of magnetite nanoparticles embedded in Fe4O4 @ Cavity composite microbubbles, the inset shows the MNPs in the mixture of water and dichloromethane, the MNPs despersed only in upper water phase.

Fig.S3CLSM images of Fe3O4@Shell composite microbubbles fabricated by varying the speed of homogenizer (rpm) and the length of homogenization time (min) during the second emulsification. Shown are Samples S6-05-13 (image a), S6-15-13 (b), S6-25-13 (c), S14-05-13 (d), S14-15-13 (e), S14-25-13 (f), S20-05-13 (g), S20-15-13 (h) and S20-25-13 (i). The shells of the microbubbles were stained with rhodamine B. The images at the upper left inset corner describe the influence of the homogenization speed and homogenization time on controlling the morphology of the Fe3O4@Shell composite microbubbles.

Shown inFig.S3 are the CLSM images of products fabricated at various homogenizer speeds after different homogenization durations. As disclosed by the CLSM study, at a speed of 6,000 rpm, with the homogenization times ranging from 0.5 min, to 1.5 min, and finally to 2.5 min, the inner structures of resultant particlesvaried respectively from “honeycomb” (Fig.S3a), to “multicavity” (Fig.S3b), and finally to “concentric single cavity”(Fig.S3c) structures. In addition, increases of homogenization time were accompanied with decreases of the average particle size. When the speed of the homogenizer was increased to 14,000 rpm, the morphologies of the resultant products obtained at 0.5, 1.5, and 2.5 min were respectively “honeycomb” (Fig.S3d), “eccentric” (Fig.S3e), and “crater” (Fig.S3f) structures. Meanwhile at the highest speed of 20,000 rpm, the products prepared at 0.5 min had already formed “single cavity” microbubbles (Fig.S3g). With increasing homogenization times, these structures then formed“bowl-like” (Fig.S3h) and solid structures (Fig.S3i). In addition, the internal structures of microbubbles prepared atincreasing homogenization speeds but with the same homogenization time were compared. In this case, their morphology also changed from “honeycomb”to “single cavity”, and finally to solid structures. This behavior followeda similar trendto that observed with increasing lengths of homogenization time. Accordingly, the structural variation among the products obtained with increasing homogenization speed and duration in the second emulsion are illustrated by the scheme shown in the upper left corner in Fig.S3.

As shown in the inset of Fig.S3, field emission scanning electron microscopy (FE-SEM, JEOL JSM-7401F) was used to examine the surface morphology of the composite microbubbles. For SEM observation, the dried microbubbles were coated with a thin layer of gold and were observed at 5.0 kV.

The formation and transformation of these different morphologies can be rationalized by the proposed mechanism as follows. At the early stages of the second emulsion, the larger oil droplets can capture more than one inner aqueous droplet,and consequently“honeycomb” or “multicavity” microbubbles are formed. Increasing the speed of the homogenizer or prolonging the homogenizationduration causes the oil droplets to break down into smaller droplets capturing only one inner aqueous droplet, subsequently yielding “single cavity”microbubbles. If the homogenization speed is too high or its duration is too long, the inner aqueous droplets tend to escape from the oil droplets to the outer aqueous phase.1 The “eccentric”, “bowl-like” and “crater-like”products resulted from this escaping process. After the inner aqueous droplets completely escape from the oil droplets, the W1/O/W2 double emulsion transforms to an O/W emulsion, and thus solid microparticles are obtained after solvent evaporation.

Fig.S4 TGA curves of (a) Fe3O4@Cavity microbubbles and (b) Fe3O4@Shell microbubbles at diffterent magnetite content.

The diameters of the microbubbles were measured using a LS13 320 Laser Diffraction Particle Size Analyzer (Beckman CoulterLtd., USA).

Fig. S5Size distribution of (a) Fe3O4@cavity microbubbles and (b) Fe3O4@shell microbubbles.

Fig. S6 The room temperature hysteresis loops of two types of Fe3O4 inside themicrobubbles