Research ArticleHEALTH AND MEDICINE

Protein-avoidant ionic liquid (PAIL)–coated nanoparticles to increase bloodstream circulation and drive biodistribution

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Science Advances  25 Nov 2020:
Vol. 6, no. 48, eabd7563
DOI: 10.1126/sciadv.abd7563
  • Fig. 1 An ionic liquid was used to successfully coat PLGA NPs.

    (A) 1H NMR spectrum of PLGA NPs surface coated with choline hexenoate (1:2). (B) DLS reported hydrodynamic diameter of NPs (log10 transformation on the x axis) when bare (black), coated with PEG (blue), and coated with IL (red) with mean diameters above each curve. (C) DLS reported zeta potential of NPs when bare (black), coated with PEG (blue), and coated with IL (red). (D) TEM of bare PLGA particles. (E) TEM of PEG-capped particles. (F) TEM of IL-coated particles. Scale bars, 200 nm.

  • Fig. 2 Choline hexenoate–coated NPs retain integrity in mouse serum, retaining their size and surface charge, and show limited hemolysis.

    (A) Relative percentage increase in NP hydrodynamic diameter over time in serum from original size by DLS (n = 4), with bare NPs shown in black, PEGylated NPs in blue, and PAIL-NPs in red. (B) Zeta potential (n = 3) measured at the final time point, showing that PEG and PAIL-capped particles have a similar surface charge. (C) SDS-PAGE from a 12% gel with tris-Gly running buffer. Left to right: Ladder, PLGA 2 min, PLGA 20 min, PEG 2 min, PEG, 20 min, IL 2 min, IL 20 min. (D) Hemolysis (n = 4) of mouse RBCs in vitro show ILs do not induce significantly more hemolysis than controls (one-way ANOVA, P = 0.9586, F = 0.0425). All experiments were performed ex vivo with at least duplicate internal readings/sample/trial. All error bars are reported in SEM.

  • Fig. 3 IL-coated NPs show the highest retention in the bloodstream at 24 hours, with directed biodistribution to the lungs and the lowest IL-6 levels of all NP groups.

    (A) Mouse 24-hour in vivo bloodstream circulation profile. Percentage of tail vein–injected dose measured at each time point, with bare particles in black, PEG coated in blue, and IL coated in red. n = 6. IL-coated particles outperform PEG particles and are significantly more highly detected than uncoated PLGA NPs at 24 hours (one-way ANOVA; 24 hours: P = 0.000031, F = 22.47, followed by t test: paired two-tailed sample for means: P = 0.00202). (B) In vivo organ biodistribution profile of NPs at 24 hours by major blood-filtering organs. Represented as percentage of tail vein–injected dose. Inset shows the direct [lung:liver] ratio of the IL, PEG, and bare NPs. n = 6, ***P < 0.001,**P < 0.01, and *P < 0.05 (one-way ANOVA verified by t test: paired two-tailed sample for means). (C) Twenty-four hours post IV injection activated in vivo mouse IL-6 concentrations in the plasma (pg/ml). (n = 4), t test: paired two-tailed sample for means: **P < 0.005, ***P < 0.001, and ****P < 0.0001. (D) Representative IVIS images of whole major blood-filtering organs at 24 hours after injection. All error bars are reported as standard error of the mean.

  • Fig. 4 PAIL-NPs adhere to RBCs in vivo.

    (A to D) SEM of RBCs withdrawn from mice after being treated with (A) bare PLGA NPs, (B) PEG-PLGA NPs, and (C) PAIL-NPs. (D) PAIL-NPs treated in vitro. Scale bars, 400 nm. Black arrows indicate NPs. (E and F) FACS 24 hours after injection of (E) bare NPs RBCs, (F) bare NPs in plasma, (G) PAIL-NPs in RBCs, and (H) PAIL-NPs in plasma.

Supplementary Materials

  • Supplementary Materials

    Protein-avoidant ionic liquid (PAIL)–coated nanoparticles to increase bloodstream circulation and drive biodistribution

    Christine M. Hamadani, Morgan J. Goetz, Samir Mitragotri, Eden E. L. Tanner

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    This PDF file includes:

    • Supplementary Materials
    • IL volume optimization
    • Tables S1 and S2
    • Figs. S1 to S7

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