The Influence of Vesicle Shape and Medium Conductivity on Possible Electrofusion under a Pulsed Electric Field - Fig 3

<p>(Color online) <b>TMV and pore density versus central angle (<i>θ</i>, from left to right) for oblate (<i>k</i> = 1/2), spherical (<i>k</i> = 1), and prolate (<i>k</i> = 2) vesicles in medium with conductivity 1 S/m at <i>t</i> = 0.4 <i>μs</i> (a, b) and 0.01 S/m at <i>t</i> = 4 <i>μs</i> (c, d)</b> with electric field of 1.5 kV/cm. The dash color lines (in a, c) represent TMV without eletroporation and the corresponding solid color lines represent TMV with electroporation. Thin horizontal lines in (<i>b</i>) and (<i>d</i>) indicate a pore density of 10¹³ <i>m</i>⁻².</p

Model of two contact vesicles with axis ratios (<i>k</i> = 1/2) exposed to an electric field.

<p>The axis ‘a’ is parallel to the direction of electric field (also the axis of symmetry). The magnitude of electric field (1.5 kV/cm) is determined as the potential difference between the two electrodes (electrode potential), divided by the electrode distance. The direction of the electric field is indicated with an arrow. Polar angle <i>θ</i>₁ for the left vesicle arises along the clockwise direction, whereas polar angle <i>θ</i>₂ for the right vesicle arises along the counterclockwise direction.</p

Variations of vesicle geometries used for analysis.

<p>The dash lines in the oblate vesicle represent its axes <i>x</i> and <i>z</i>. The applied external electric field is along the <i>x</i>-axis of the vesicles. The axis ratio (<i>k</i> = <i>a</i>/<i>c</i>) used here is equal to 1/2, 1, and 2, respectively, and <i>θ</i> is the polar angle, measured along the clockwise direction. <i>σ</i>_<i>i</i>, <i>σ</i>_<i>m</i>, <i>σ</i>_<i>e</i> and <i>ε</i>_<i>i</i>, <i>ε</i>_<i>m</i>, <i>ε</i>_<i>e</i> are the conductivities and permittivities of internal solution, membrane and external solution.</p

Parameters used in calculation.

<p>Parameters used in calculation.</p

Calculation of TMV of two equally sized spheroidal vesicles with different axis ratios after the onset of exposure to a 1.5 kV/cm pulsed electric field.

<p>The results show that TMV and pore density as a function of central angle (left vesicle <i>θ</i>₁, right vesicle <i>θ</i>₂), in the medium condition <i>σ</i>_<i>i</i> < <i>σ</i>_<i>e</i> (<i>σ</i>_<i>i</i> = 0.2 S/m, <i>σ</i>_<i>e</i> = 1 S/m) at <i>t</i> = 0.5 <i>μs</i> (a, b) and <i>σ</i>_<i>i</i> > <i>σ</i>_<i>e</i> (<i>σ</i>_<i>i</i> = 0.2 S/m, <i>σ</i>_<i>e</i> = 0.01 S/m) at <i>t</i> = 1 <i>μs</i> (c, d). The contact areas are marked with the vertical line. Thin horizontal lines in (<i>b</i>) and (<i>d</i>) indicate a pore density of 10¹³ <i>m</i>⁻².</p

Calculated time evolution of pore density at the point of pole and at the contact area between two equally oblate shape vesicles (a to d) and prolate shape vesicles (e to g) in a pulsed electric field with 1.5 kV/cm.

<p>The pulse duration time limits to 1 <i>μs</i>, 2 <i>μs</i>, 10 <i>μs</i>, and 100 <i>μs</i> with corresponding external medium conductivity 1 S/m (a, e), 0.1 S/m (b, f), 0.01 S/m (c, g), and 10⁻³ S/m (d, h), respectively. Note that the time is presented on a logarithmic scale as this allows one to study the pore generation in the nanosecond and microsecond range simultaneously. The thin horizontal lines indicate a pore density of 10¹³ <i>m</i>⁻².</p

Biodegradable Nanoglobular Magnetic Resonance Imaging Contrast Agent Constructed with Host–Guest Self-Assembly for Tumor-Targeted Imaging

Gadolinium-based macromolecular magnetic resonance imaging (MRI) contrast agents (CAs) have attracted increasing interest in tumor diagnosis. However, their practical application is potentially limited because the long-term retention of gadolinium ion in vivo will induce toxicity. Here, a nanoglobular MRI contrast agent (CA) PAMAM-PG-<i>g</i>-s-s-DOTA­(Gd) + FA was designed and synthesized on the basis of the facile host–guest interaction between β-cyclodextrin and adamantane, which initiated the self-assembly of poly­(glycerol) (PG) separately conjugated with gadolinium chelates by disulfide bonds and folic acid (FA) molecule onto the surface of poly­(amidoamine) (PAMAM) dendrimer, finally realizing the biodegradability and targeting specificity. The nanoglobular CA has a higher longitudinal relaxivity (<i>r</i>₁) than commercial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), showing a value of 8.39 mM^–1 s^–1 at 0.5 T, and presents favorable biocompatibility on the observations of cytotoxicity and tissue toxicity. Furthermore, MRI on cells and tumor-bearing mice both demonstrate the obvious targeting specificity, on the basis of which the effective contrast enhancement at tumor location was obtained. In addition, this CA exhibits the ability of cleavage to form free small-molecule gadolinium chelates and can realize minimal gadolinium retention in main organs and tissues after tumor detection. These results suggest that the biodegradable nanoglobular PAMAM-PG-<i>g</i>-s-s-DOTA­(Gd) + FA can be a safe and efficient MRI CA for tumor diagnosis