DETECTION OF FORMATION AND DISINTEGRATION OF MICELLES BY OBLIQUE-INCIDENCE REFLECTIVITY DIFFERENCE MICROSCOPY

An oblique-incidence reflectivity difference (OI-RD) scanning microscope was developed for label-free detection of the formation and disintegration of micelles upon solid substrates. Micelles are made of polymers with hydrophilic heads in contact with the surrounding solvent and hydrophobic tails in the micelle center. This characteristic makes them very efficient drug carriers. Streptavidin molecules were first printed on glass slides for capturing biotinylated polymers. Micelles were formed when the concentration of polymers was higher than a critical value. The formation of micelles resulted in an increase in the oblique-incidence reflectivity difference signals. As the concentration of polymers decreased below the critical value, micelles were disintegrated, and a corresponding decrease in the oblique-incidence reflectivity difference signals was observed. This microscope was employed for the real-time monitoring of the formation and disintegration of two different micelles. The critical concentration above which micelles were formed was determined to be around 0.0006 mg/mL for micelles made of PEG5KCA8 polymers. The results suggest that this microscope would have practical application in testing the efficiency and durability of micellar drug carriers.

[1]  S. L. Bud'ko,et al.  Anomalous temperature-dependent transport in YbNi2B2C and its correlation to microstructural features , 2004 .

[2]  K. Lam,et al.  Oblique-incidence reflectivity difference microscope for label-free high-throughput detection of biochemical reactions in a microarray format. , 2006, Applied optics.

[3]  R. Gurny,et al.  Biodegradable nanoparticles for direct or two-step tumor immunotargeting. , 2006, Bioconjugate chemistry.

[4]  J. L. Turner,et al.  Folic acid-conjugated nanostructured materials designed for cancer cell targeting. , 2003, Chemical communications.

[5]  J P Landry,et al.  Label-free detection of microarrays of biomolecules by oblique-incidence reflectivity difference microscopy. , 2004, Optics letters.

[6]  K. Kataoka,et al.  Block copolymer micelles for drug delivery: design, characterization and biological significance. , 2001, Advanced drug delivery reviews.

[7]  Y.S. Sun,et al.  Effect of fluorescently labeling protein probes on kinetics of protein-ligand reactions , 2008, 2008 Conference on Lasers and Electro-Optics and 2008 Conference on Quantum Electronics and Laser Science.

[8]  D. Lasič,et al.  Doxorubicin in sterically stabilized liposomes , 1996, Nature.

[9]  Kit S Lam,et al.  Well-defined, reversible disulfide cross-linked micelles for on-demand paclitaxel delivery. , 2011, Biomaterials.

[10]  Lining Gao,et al.  A surfactant type fluorescence probe for detecting micellar growth. , 2011, Journal of colloid and interface science.

[11]  S. Fukushima,et al.  Cyclic RGD peptide-conjugated polyplex micelles as a targetable gene delivery system directed to cells possessing alphavbeta3 and alphavbeta5 integrins. , 2007, Bioconjugate chemistry.

[12]  I. Chaiken,et al.  Interpreting complex binding kinetics from optical biosensors: a comparison of analysis by linearization, the integrated rate equation, and numerical integration. , 1995, Analytical biochemistry.

[13]  Kit S Lam,et al.  Well-defined, size-tunable, multifunctional micelles for efficient paclitaxel delivery for cancer treatment. , 2010, Bioconjugate chemistry.

[14]  Colloidal Aggregate Detection by Rapid Fluorescence Measurement of Liquid Surface Curvature Changes in Multiwell Plates , 2007, Journal of biomolecular screening.

[15]  T. Okano,et al.  Inner core segment design for drug delivery control of thermo-responsive polymeric micelles. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Li Liu,et al.  Bioconjugation of biotin to the interfaces of polymeric micelles via in situ click chemistry. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[17]  N. Turro,et al.  Fluorescence probes for critical micelle concentration determination. , 1985, Langmuir : the ACS journal of surfaces and colloids.

[18]  R. Duncan,et al.  Drug-polymer conjugates: potential for improved chemotherapy. , 1992, Anti-cancer drugs.

[19]  C. Y. Fong,et al.  An oblique-incidence optical reflectivity difference and LEED study of rare-gas growth on a lattice-mismatched metal substrate , 2004 .

[20]  Xiangdong Zhu Oblique-incidence optical reflectivity difference from a rough film of crystalline material , 2004 .

[21]  S. W. Kim,et al.  Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Kit S Lam,et al.  The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles. , 2011, Biomaterials.

[23]  Drug release from thermo-responsive self-assembled polymeric micelles composed of cholic acid and poly(N-isopropylacrylamide) , 2000, Archives of pharmacal research.

[24]  S. Fukushima,et al.  Cyclic RGD Peptide-Conjugated Polyplex Micelles as a Targetable Gene Delivery System Directed to Cells Possessing αvβ3 and αvβ5 Integrins , 2007 .

[25]  R. Gurny,et al.  In Vitro Extended-Release Properties of Drug-Loaded Poly(DL-Lactic Acid) Nanoparticles Produced by a Salting-Out Procedure , 1993, Pharmaceutical Research.

[26]  T. Okano,et al.  Preparation and characterization of the micelle-forming polymeric drug indomethacin-incorporated poly(ethylene oxide)-poly(beta-benzyl L-aspartate) block copolymer micelles. , 1996, Journal of pharmaceutical sciences.

[27]  J P Landry,et al.  Macromolecular scaffolds for immobilizing small molecule microarrays in label-free detection of protein-ligand interactions on solid support. , 2009, Analytical chemistry.

[28]  M. Becker,et al.  Synthesis, characterization, and bioavailability of mannosylated shell cross-linked nanoparticles. , 2004, Biomacromolecules.

[29]  M. Jones,et al.  Polymeric micelles - a new generation of colloidal drug carriers. , 1999, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[30]  Y. Nagasaki,et al.  Sugar-installed block copolymer micelles: their preparation and specific interaction with lectin molecules. , 2001, Biomacromolecules.

[31]  G. Spenlehauer,et al.  Biodegradable microparticles for delivery of polypeptides and proteins. , 1989, Progress in clinical and biological research.

[32]  Kam W Leong,et al.  Thermally responsive polymeric micellar nanoparticles self-assembled from cholesteryl end-capped random poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide): synthesis, temperature-sensitivity, and morphologies. , 2003, Journal of colloid and interface science.

[33]  Teruo Okano,et al.  Preparation and Characterization of the Micelle-Forming Polymeric Drug Indomethacin-lncorporated Polyfethylene oxide)-Poly(β-benzyl L-aspartate) Block Copolymer Micelles , 1996 .

[34]  Thermo-responsive self-assembled polymeric micelles for drug delivery in vitro. , 2000, International journal of pharmaceutics.

[35]  J. Fréchet,et al.  Stimuli-responsive supramolecular assemblies of linear-dendritic copolymers. , 2004, Journal of the American Chemical Society.

[36]  T. Okano,et al.  Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate). , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[37]  R. Zhuo,et al.  Biotinylated thermoresponsive micelle self-assembled from double-hydrophilic block copolymer for drug delivery and tumor target. , 2008, Biomaterials.

[38]  N. Nishiyama,et al.  In vivo antitumor activity of the folate-conjugated pH-sensitive polymeric micelle selectively releasing adriamycin in the intracellular acidic compartments. , 2007, Bioconjugate chemistry.

[39]  You Han Bae,et al.  Super pH-sensitive multifunctional polymeric micelle. , 2005, Nano letters.

[40]  J P Landry,et al.  Protein reactions with surface-bound molecular targets detected by oblique-incidence reflectivity difference microscopes. , 2008, Applied optics.