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In situ formation of magnetopolymersomes via electroporation for MRI.

ABSTRACT: As the development of diagnostic/therapeutic (and combined: theranostic) nanomedicine grows, smart drug-delivery vehicles become ever more critical. Currently therapies consist of drugs tethered to, or encapsulated within nanoparticles or vesicles. There is growing interest in functionalising them with magnetic nanoparticles (MNPs) to target the therapeutics by localising them using magnetic fields. An alternating magnetic field induces remote heating of the particles (hyperthermia) triggering drug release or cell death. Furthermore, MNPs are diagnostic MRI contrast agents. There is considerable interest in MNP embedded vehicles for nanomedicine, but their development is hindered by difficulties producing consistently monodisperse MNPs and their reliable loading into vesicles. Furthermore, it is highly advantageous to "trigger" MNP production and to tune the MNP's size and magnetic response. Here we present the first example of a tuneable, switchable magnetic delivery vehicle for nanomedical application. These are comprised of robust, tailored polymer vesicles (polymersomes) embedded with superparamagnetic magnetite MNPs (magnetopolymersomes) which show good MRI contrast (R2* = 148.8 s(-1)) and have a vacant core for loading of therapeutics. Critically, the magnetopolymersomes are produced by a pioneering nanoreactor method whereby electroporation triggers the in situ formation of MNPs within the vesicle membrane, offering a switchable, tuneable magnetic responsive theranostic delivery vehicle.

SUBMITTER: Bain J

PROVIDER: S-EPMC4585761 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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In situ formation of magnetopolymersomes via electroporation for MRI.

Bain Jennifer J Ruiz-Pérez Lorena L Kennerley Aneurin J AJ Muench Stephen P SP Thompson Rebecca R Battaglia Giuseppe G Staniland Sarah S SS

Scientific reports 20150922

As the development of diagnostic/therapeutic (and combined: theranostic) nanomedicine grows, smart drug-delivery vehicles become ever more critical. Currently therapies consist of drugs tethered to, or encapsulated within nanoparticles or vesicles. There is growing interest in functionalising them with magnetic nanoparticles (MNPs) to target the therapeutics by localising them using magnetic fields. An alternating magnetic field induces remote heating of the particles (hyperthermia) triggering d ...[more]

PMID: 26391797

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Project description:BackgroundHigh-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo.MethodsTen Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student's t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch's ANOVA test followed by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn's multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables.ResultsHigher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 vs. 0.08 ± 0.05, t = 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 (P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cm2vs. 3.20 ± 0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm2vs. 1.30 ± 0.50 cm2, t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 vs. 0.73 ± 0.06 vs. 0.68 ± 0.07, F = 241.300, P < 0.001) and heat shock protein 70 (HSP70) (0.03 ± 0.01 vs. 0.46 ± 0.09 vs. and 0.42 ± 0.07, F = 64.490, P < 0.001) were significantly different between the untreated, IRE and H-FIRE zones, but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone (both P > 0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ± 3.77°C vs. 16.20 ± 7.45°C, t = 0.682, P = 0.504). The Ktrans value (r = 0.940, P = 0.017) and the Kep value (r = 0.895, P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.ConclusionsH-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.

Project description:PurposeAblation plays a growing role in the treatment of small renal masses (SRMs) due to its nephron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the potential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow up after renal IRE in humans. Objectives are to assess computed tomography (CT) and magnetic resonance imaging (MRI) on the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE.MethodsProspective phase 2 study of IRE in nine patients with ten SRMs. MRI imaging was performed pre-IRE, 1 week, 3 months, 6 months and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and relation between the needle configuration volume (NCV; planned AZV) and CT- and MRI volumes were evaluated.ResultsEight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a non-diagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (respectively, 16.8 cm3 and 6.2 cm3) compared to the NCV (4.8 cm3). On MRI, median AZV increased 1-week post-IRE until 3 months post-IRE (respectively, 14.5 cm3 and 4.6 cm3) compared to the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm3; MRI 3.0 cm3), continuing at 12 months (CT 4.2 cm3, MRI 1.1 cm3). Strong correlation was demonstrated between the planning and the post-treatment volumes. Inter-observer agreement between observers was excellent (CT 95% CI 0.82-0.95, MRI 95% CI 0.86-0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumour. Subtraction images confirmed non-enhancement on MRI in unclear enhancement cases (3/9). Directly after IRE, gas bubbles, perinephric stranding and edema were observed in all cases.ConclusionThe AZV increases immediately on CT until 3 months after IRE. On MRI, the AZV increases at 1 week until 3 months post-IRE. At 6 months the AZV starts decreasing until 12 months post-IRE on both CT and MRI. Enhancement was absent post-IRE, except for one residual tumour. Gas bubbles, perinephric stranding and edema are normal findings directly post-IRE.

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In situ formation of magnetopolymersomes via electroporation for MRI.

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In situ formation of magnetopolymersomes via electroporation for MRI.

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