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. 2014 May 14;10(9):1719-23.
doi: 10.1002/smll.201303190. Epub 2014 Feb 25.

P-glycoprotein-dependent trafficking of nanoparticle-drug conjugates

Erik C Dreaden  1 , Idris O Raji, Lauren A Austin, Shaghayegh Fathi, Sandra C Mwakwari, William H Humphries 4th, Bin Kang, Adegboyega K Oyelere, Mostafa A El-Sayed
Affiliations

P-glycoprotein-dependent trafficking of nanoparticle-drug conjugates

Erik C Dreaden et al. Small. .
No abstract available

Keywords: colloids; gold; nanoparticles; nanorods; nanotechnology.

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Figures

Figure 1
Figure 1
a ) Illustration of model drug carriers used to investigate ligand-dependent cellular trafficking of nanoparticle-drug conjugates. Gold nanorods were functionalized with mixed self-assembled monolayers of thiolated poly(ethylene glycol) (PEG) and one of three thiol PEGylated substrates of P-gp that exhibit varying degrees of interaction with the protein. b) Spectroscopic and structural characterization (inset) of the nanoparticles indicating high purity and monodispersity by UV-Vis absorption spectroscopy and transmission electron microscopy, respectively. c ) Cellular uptake of the nanoparticle conjugates in P-gp expressing RAW264.7 monocytes indicating concentration- and ligand-dependent cellular accumulation (24 h). d) Confocal fluorescence microscopy of dye-labeled nanoparticle conjugates (green) indicating co-localization with endo/lysosomal markers (red). L/T represents the intensity ratio between the longitudinal and transverse plasmon bands of the nanorods, a comparative metric which reflects the relative amount of impurity contributions from nanospheres. Error bars represent SD of ten technical replicates. Scale bar, (b) 50 nm, (d) 10 μm.
Figure 2
Figure 2
P-gp- and ligand-dependent changes in nanoparticle accumulation following co-incubation with P-gp-competitive inhibitors. Net changes in nanoparticle accumulation in (a ) P-gp null COLO 205 and ( b) P-gp-expressing J774.2 cells incubated with P-gp substrate-conjugated gold nanorods and the inhibitor cyclosporine (red) or verapamil (blue). c) Darkfield scattering microscopy of cells in (b) indicating ligand-dependent changes in particle accumulation in the presence of competitive P-gp inhibitors. Bright field images are overlayed in (c). Error bars represent SD of three biological replicates. P≤ *0.05, **0.01. Scale bar, 10 μm.
Figure 3
Figure 3
Real-time efflux kinetics of P-gp substrate-conjugated nanoparticles. J774.2 cells were loaded with 0.01 nM azithromycin-gold nanorods for 24 h, after which nanoparticle-containing media was removed and replaced by fresh media spiked with the P-gp-competitive inhibitor verapamil. a ) Live-cell dark-field scattering microscopy and (b) quantitative image analysis of nanoparticle cell efflux kinetics in the presence and absence of verapamil. ISCA represents the relative background-subtracted scattering intensity of the nanoparticles. Error in (b) is plotted as SEM of mean pixel intensity per field of view and rate constants represent mean ± SD of a one-phase exponential fit. Scale bar, 100 μm.
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References

    1. Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G. Science. 2009;323:1718. - PMC - PubMed
    1. Goldman B. J Natl Cancer Inst. 2003;95:255. - PubMed
    1. Kannan P, Brimacombe KR, Kreisl WC, Liow JS, Zoghbi SS, Telu S, Zhang Y, Pike VW, Halldin C, Gottesman MM, Innis RB, Hall MD. Proc Natl Acad Sci USA. 2011;108:2593. - PMC - PubMed
    1. Zavaleta CL, Smith BR, Walton I, Doering W, Davis G, Shojaei B, Natan MJ, Gambhir SS. Proc Natl Acad Sci USA. 2009;106:13511. - PMC - PubMed
    2. Zavaleta C, Garai E, Liu J, Sensarn S, Mandella M, Van de Sompel D, Friedland S, Van Dam J, Contag C, Gambhir S. Proc Natl Acad Sci U S A. 2013;110:97. - PMC - PubMed
    3. Cheng Y, Samia AC, Meyers JD, Panagopoulos I, Fei B, Burda C. J Am Chem Soc. 2008;130:10643. - PMC - PubMed
    4. Cheng Y, Meyers JD, Broome AM, Kenney ME, Basilion JP, Burda C. J Am Chem Soc. 2011;133:2583. - PMC - PubMed
    5. Hauck TS, Ghazani AA, Chan WCW. Small. 2008;4:153. - PubMed
    6. Kim BYS, Rutka JT, Chan WCW. New Engl J Med. 2010;363:2434. - PubMed
    7. Lohse S, Murphy C. J Am Chem Soc. 2012;134:15607. - PubMed
    8. Murphy CJ, Gole AM, Stone JW, Sisco PN, Alkilany AM, Goldsmith EC, Baxter SC. Acc Chem Res. 2008;41:1721. - PubMed
    9. Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA. Chem Soc Rev. 2012;41:2740. - PMC - PubMed
    1. Libutti SK, Paciotti GF, Byrnes AA, Alexander HR, Gannon WE, Walker M, Seidel GD, Yuldasheva N, Tamarkin L. Clin Cancer Res. 2010;16:6139. - PMC - PubMed

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