Biopolym. Cell. 2014; 30(4):314-320.
Bioorganic Chemistry
Dynamics of dye release from nanocarriers of different types in model cell membranes and living cells
1Tkacheva T. N., 1Yefimova S. L., 1Klochkov V. K., 1Sorokin A. V., 1Malyukin Yu. V.
  1. Institute for Scintillation Materials, NAS of Ukraine
    60, Lenin Ave., Kharkiv, Ukraine, 61001


Aim. To study the dynamics of lipophilic content release from nanocarriers of different types, organic molecular ensembles and inorganic nanoparticles (NPs) in vitro experiments. Methods. Two-channel ratiometric fluorescence detection method based on Forster Resonance Energy Transfer, fluorescent spectroscopy and micro-spectroscopy have been used. Results. It has been found that the profiles of lipophilic dyes release from organic nanocarriers (PC liposomes and SDS micelles) and inorganic ones (GdYVO4:Eu3+ and CeO2 NPs) are well fitted by the first-order reaction kinetics in both model cell membranes and living cells (rat hepatocytes). The dye release constants (K) and half-lives (t1/2) were analyzed. Conclusions. GdYVO4:Eu3+ and CeO2 NPs have been shown to provide faster lipophilic content release in model cell membranes as compared to PC liposomes. Negatively charged or lipophilic compounds added into nanocarriers can decrease the rate of lipophilic dyes release. Specific interaction of GdYVO4:Eu3+ NPs with rat hepatocytes has been observed.
Keywords: nanocarries, Forster Resonance Energy Transfer, dye release, model cell membranes, living cells


[1] Hunziker P. Nanomedicine: shaping the future of medicine. Eur J Nanomed. 2012;2(1):4.
[2] Bamrungsap S, Zhao Z, Chen T, Wang L, Li C, Fu T, Tan W. Nanotechnology in therapeutics: a focus on nanoparticles as a drug delivery system. Nanomedicine (Lond). 2012;7(8):1253-71.
[3] Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine. 2012;8(2):147-66.
[4] Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J. 2007;9(2):E128-47.
[5] Liu Y, Niu T-S, Zhang L, Yang J-S. Review on nano-drugs. Natural Science. 2010; 2(1); 41–8.
[6] Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761-9.
[7] Klochkov VK. Coagulation of luminescent colloid nGdVO4:Eu solutions with inorganic electrolytes. Functional Materials. 2009; 16(2):141–4.
[8] Tkacheva TN, Yefimova SL, Klochkov VK, Sorokin AV, Borovoy IA, Malyukin YuV. Spectroscopic study of inorganic nanopartic- les nGdYVO4:Eu3+ and organic carbocyanin dyes interactions in aqueous solutions. Biophysical Bulletin. 2012; 1: 12–9.
[9] Klochkov VK, Grigorova AV, Sedyh OO, Malyukin YuV. The influence of agglomeration of nanoparticles on their superoxide dismutase-mimetic activity. Colloids Surf A Physicochem Eng Asp. 2012; 409:176–82.
[10] Klochkov V, Kavok N, Grygorova G, Sedyh O, Malyukin Y. Size and shape influence of luminescent orthovanadate nanoparticles on their accumulation in nuclear compartments of rat hepatocytes. Mater Sci Eng C Mater Biol Appl. 2013;33(5):2708–12.
[11] Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001;73(2-3):121-36.
[12] Lakowicz JR. Principles of fluorescence spectroscopy. New York etc., Kluwer Acad. Plenum Publ., 1999; 698 p.
[13] Demchenko AP. The concept of λ-ratiometry in fluorescence sensing and imaging. J Fluoresc. 2010;20(5):1099-128.
[14] Yefimova SL, Lebed AS, Guralchuk GYa, Sorokin AV, Kurilchenko IYu, Kavok NS, Malyukin YuV. Nano-scale liposomal container with a «signal system» for substances delivering in living cells. Biopolym Cell. 2011; 27(1):47–52.
[15] Yefimova SL, Kurilchenko IYu., Tkacheva TN, Kavok NS, Todor IN, Lukianova NYu, Chekhun VF, Malyukin YuV. Microspectro- scopic study of liposome-to-cell interaction revealed by Forster resonance energy transfer. J Fluoresc. 2014; 24(2):403–9.
[16] Mui B, Chow L, Hope MJ. Extrusion technique to generate liposomes of defined size. Methods Enzymol. 2003;367:3-14.
[17] Wang SR, Renaud G, Infante J, Catala D, Infante R. Isolation of rat hepatocytes with EDTA and their metabolic functions in primary culture. In Vitro Cell Dev Biol. 1985;21(9):526-30.
[18] Chen H, Kim S, He W, Wang H, Low PS, Park K, Cheng JX. Fast release of lipophilic agents from circulating PEG-PDLLA micelles revealed by in vivo forster resonance energy transfer imaging. Langmuir. 2008;24(10):5213-7.
[19] Chen H, Kim S, Li L, Wang S, Park K, Cheng JX. Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Forster resonance energy transfer imaging. Proc Natl Acad Sci U S A. 2008;105(18):6596-601.
[20] Lu J, Owen SC, Shoichet MS. Stability of Self-Assembled Polymeric Micelles in Serum. Macromolecules. 2011;44(15):6002-6008.
[21] Torchilin V, Weissig V. Liposomes. A practical approach. New York: Oxford Univ. Press, 2003; 396 p.
[22] Pasa G, Mishra US, Tripathy NK, Sahoo SK, Mahapatra AK. Formulation development and evoluation of didanosine sustai- ned-release matrix tablets using HPMC K15. Int J Pharm. 2012; 2(1):97–100.
[23] Fundamentals and applications of controlled release drug delivery. Eds J Siepmann, RA Siegel, MJ Rathbone. Advances in Delivery Science and Technology. Springer, 2012; 19–43.
[24] Griffith LG. Polymeric biomaterials. Acta Mater. 2000; 48(1):263–77.