Dokument

Summary:
Topic of the presented work is the preparation of multifunctional polymer microcapsules for biological and biomedical applications. The fabrication of such capsules is based on the layered adsorption of oppositely charged polymers, the so-called polyelectrolytes, onto charged templates (layer-by-layer assembly). As spherical base for the capsules porous calcium carbonate particles have been used. In addition to molecules that were encapsulated into the final polymer capsules further properties such as fluorescence, paramagnetic behavior or the ability to convert light energy into heat were embedded into the polymer shell by implementing nanoparticles. These functional groups were crucial for the realization of the experimental demands on the microsystems. In addition to the functionalization of the shell an efficient filling of the capsules with a multitude of different molecules was one of the major developments. Besides a coprecipitation method (pre-filling of the templates), a post-loading technique as well as the enrichment of the capsules with amphiphilic polymer micelles were used for loading the capsules. This last approach even allowed for filling both, hydrophilic and hydrophobic molecules into the the polymer microcapsules. The prepared materials were observed via absorbance or fluorescence spectroscopy or electron- and optical microscopy, the capsules were tested specifically for their intended applications. Here, special emphasis was placed on the intracellular release of the encaged cargo materials. Numerous experiments were performed to test the release of the cargo molecules within living cells. The efficient release via external laser-triggered heating was proven and improved by variation of gold-nanoparticle concentration attached to the polymer shells. In addition, the released content distributed into the cells, was observed to react after its liberation. Reactive substances, which have been separately encapsulated could successfully be released intracellularly and the occurring reactions were detected. Furthermore, nucleic acid chains (mRNA) could be encapsulated and successfully be released within cells. The cellular production of the RNA-encoded proteins was demonstrated. Another aim of the study was the targeted delivery of capsules to a desired place. In a flow chaannel, the flow of blood in living organisms was simulated. Capsules modified with ironoxide nanoparticles could be deposited selectively on a cell layer with the help of magnetic field gradients. This enabled for deposition of capsules on a large scale area as well as on on small, sub-millimeter patterns. Additionally to the release of materials and controlled deposition of capsules, the presented work is also studying the possible use of microcapsules as sensors for the composition of the environmental solution. These sensor properties were tested on the basis of ion-selective fluorescent dyes in the extracellular as well as in the intracellular space. In summary, the presented polymer microcapsules were proven as an advanced and versatile approach towards bio-medical requirements for drug delivery and sensing applications.

Bibliographie / References

1. A.L. Becker, A.P.R. Johnston, F. Caruso, Layer-by-layer-assembled capsules and films for therapeutic delivery, Small 6 (17) (2010) 1836–1852.
2. de la Presa, Magnetic capsules for NMR imaging: effect of magnetic nanoparticles spatial distribution and aggregation, J. Phys. Chem. C 115 (14) (2011) 6257–6264.
3. N.W. Kam, H. Dai, Carbon nanotubes as intracellular protein transporters: gener- ality and biological functionality, J. Am. Chem. Soc. 127 (16) (2005) 6021–6026.
4. A.M. Pavlov, V. Saez, A. Cobley, J. Graves, G.B. Sukhorukov, T.J. Mason, Controlled protein release from microcapsules with composite shells using high frequency ultrasound-potential for in vivo medical use, Soft Matter 7 (9) (2011) 4341–4347.
5. J.-R. Huang, T.D. Craggs, J. Christodoulou, S.E. Jackson, Stable intermediate states and high energy barriers in the unfolding of GFP, J. Mol. Biol. 370 (2) (2007) 356–371.
6. del-Mercato, L. L.; Abbasi, A. Z.; Parak, W. J. Synthesis and Characterization of Ratiometric Ion- Sensitive Polyelectrolyte Capsules. Small 2010, DOI: 10.1002/smll.201001144.
7. A.G. Skirtach, P. Karageorgiev, B. de Geest, N. Pazos-Perez, D. Braun, G.B. Sukhor- ukov, Nanorods as wavelength-selective absorption centers in the visible and Nnear-infrared regions of the electromagnetic spectrum, Adv. Mater. 20 (2008) 506–510.
8. Lee, J. A.; Mardyani, S.; Hung, A.; Rhee, A.; Klostranec, J.; Mu, Y.; Li, D.; Chan, W. C. W. Toward the Accurate Read-out of Quantum Dot Barcodes: Design of Deconvolution Algo- rithms and Assessment of Fluorescence Signals in Buffer. Adv. Mater. 2007, 19, 3113–3118.
9. Fournier-Bidoz, S.; Jennings, Travis L.; Klostranec, Jesse M.; Fung, W.; Rhee, A.; Li, D.; Chan, Warren C. W. Facile and Rapid One-Step Mass Preparation of Quantum-Dot Bar- codes. Angew. Chem., Int. Ed. 2008, 47, 5577–5581.
10. Light-Addressable Capsules as Caged Compound Matrix for Controlled Triggering of Cytosolic Reactions**
11. Kreft, O.; Prevot, M.; Mohwald, H.; Sukhorukov, G. B. Shell- in-Shell Microcapsules: A Novel Tool for Integrated, Spa- tially Confined Enzymatic Reactions. Angew. Chem., Int. Ed. 2007, 46, 5605–5608.
12. Goede, O.; Heimbrodt, W. Optical Properties of (Zn, Mn) and (Cd, Mn) Chalcogenide Mixed-Crystals and Superlattices. Phys. Status Solidi B 1988, 146, 11–62.
13. Engblom, A. C.; Akerman, K. E. O. Determination of the Intracellular Free Chloride Concentration in Rat- Brain Synaptoneurosomes Using a Chloride-Sensitive Fluorescent Indicator. Biochim. Biophys. Acta 1993, 1153, 262–266.
14. Naftalin, R. J.; Pedley, K. C. Video Enhanced Imaging of the Fluorescent Na Probe SBFI Indicates that Colonic Crypts Absorb Fluid by Generating a Hypertonic Interstitial Fluid. FEBS Lett. 1990, 260, 187–194.
15. Rivera Gil, P.; del Mercato, L. L.; del Pino, P.; Mu~ noz Javier, A.; Parak, W. J. Nanoparticle-Modified Polyelectrolyte Cap- sules. Nano Today 2008, 3,12–21.
16. Z. She, M.N. Antipina, J. Li, G.B. Sukhorukov, Mechanism of protein release from polyelectrolyte multilayer microcapsules, Biomacromolecules 11 (5) (2010) 1241–1247.
17. R. Huschka, J. Zuloaga, M.W. Knight, L.V. Brown, P. Nordlander, N.J. Halas, Light- induced release of DNA from gold nanoparticles: nanoshells and nanorods, J. Am. Chem. Soc. 133 (31) (2011) 12247–12255.
18. K. Velikov, P. Versluis, A. Popp, Interaction between biopolyelectrolytes and spar- ingly soluble mineral particles, Langmuir 27 (1) (2011) 83–90.
19. Abbasi, A. Z.; Amin, F.; Niebling, T.; Friede, S.; Ochs, M.; Romero, S. C.; Martos, J. M. M.; Rivera Gil, P.; Heimbrodt, W.; Parak, W. J. How Colloidal Nanoparticles Could Facilitate Multiplexed Measurements of Different Analytes with Analyte-Sensitive Organic Fluorophores. ACS Nano 2011, 5,21–25.
20. A. Agarwal, M.A. MacKey, M.A. El-Sayed, R.V. Bellamkonda, Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods, ACS Nano 5 (6) (2011) 4919–4926.
21. C.J. Ochs, G.K. Such, Y. Yan, M.P. van Koeverden, F. Caruso, Biodegradable click capsules with engineered drug-loaded multilayers, ACS Nano 4 (3) (2010) 1653–1663.
22. Choi, Y.; Park, Y.; Kang, T.; Lee, L. P. Selective and Sensitive Detection of Metal Ions by Plasmonic Resonance Energy Transfer-based Nanospectroscopy. Nat. Nanotechnol. 2009, 4, 742–746.
23. L.L. del Mercato, P. Rivera_Gil, A.Z. Abbasi, M. Ochs, C. Ganas, I. Zins, C. Sönnich- sen, W.J. Parak, LbL multilayer capsules: recent progress and future outlook for their use in life sciences, Nanoscale 2 (4) (2010) 458–467.
24. L.L. del Mercato, E. Gonzalez, A.Z. Abbasi, W.J. Parak, V. Puntes, Synthesis and evaluation of gold nanoparticle-modified polyelectrolyte capsules under micro- wave irradiation for remotely controlled release for cargo, J. Mater. Chem. 21 (31) (2011) 11468–11471.
25. U. Bazylinska, R. Skrzela, K. Szczepanowicz, P. Warszynski, K.A. Wilk, Novel approach to long sustained multilayer nanocapsules: influence of surfactant head groups and polyelectrolyte layer number on the release of hydrophobic compounds. Soft Matter 7 (13) (2011) 6113–6124.
26. Niebling, T.; Zhang, F.; Ali, Z.; Parak, W. J.; Heimbrodt, W. Excitation Dynamics in Polymer-Coated Semiconductor Quantum Dots with Integrated Dye Molecules: The Role of Reabsorption. J. Appl. Phys. 2009, 106, 104701.
27. R. Orij, J. Postmus, A. Ter Beek, S. Brul, G.J. Smits, In vivo measurement of cytosolic and mitochondrial pH using a pH-sensitive GFP derivative in Saccharomyces cerevisiae reveals a relation between intracellular pH and growth, Microbiology 155 (1) (2009) 268–278.
28. Nagl, S.; Stich, M. I. J.; Schaferling, M.; Wolfbeis, O. S. Method for Simultaneous Luminescence Sensing of Two Species Using Optical Probes of Different Decay Time, and its Application to an Enzymatic Reaction at Varying Temperature. Anal. Bioanal. Chem. 2009, 393, 1199–1207.
29. Nagl, S.; Wolfbeis, O. S. Optical Multiple Chemical Sensing: Status and Current Challenges. Analyst 2007, 132, 507–511.
30. Borisov, S. M.; Neurauter, G.; Schroeder, C.; Klimant, I.; Wolfbeis, O. S. Modified Dual Lifetime Referencing Method for Simultaneous Optical Determination and Sensing of Two Analytes. Appl. Spectrosc. 2006, 60, 1167–1173.
31. G. Baffou, R. Quidant, F.J. Garcia de Abajo, Nanoscale control of optical heating in complex plasmonic systems, ACS Nano 4 (2) (2010) 709–716.
32. Mikulec, F. V.; Kuno, M.; Bennati, M.; Hall, A. D.; Griffin, R. G.; Bawendi, M. G. Organometallic Synthesis and Spectroscopic Characterization of Manganese-Doped CdSe Nanocrystals. J. Am. Chem. Soc. 2000, 122, 2532–2540.
33. A.M. Pavlov, A.V. Sapelkin, X. Huang, K.M.Y. P'ng, A.J. Bushby, G.B. Sukhorukov, A.G. Skirtach, Neuron cells uptake of polymeric microcapsules and subsequent intracellular release, Macromol. Biosci. 11 (6) (2011) 848–854.
34. L.I. Kazakova, L.I. Shabarchina, G.B. Sukhorukov, Co-encapsulation of enzyme and sensitive dye as a tool for fabrication of microcapsule based sensor for urea mea- suring, Phys. Chem. Chem. Phys. 13 (23) (2011) 11110.
35. M. Bedard, B. de Geest, A. Skirtach, H. Möhwald, G. Sukhorukov, Polymeric micro- capsules with light responsive properties for encapsulation and release, Adv. Colloid Interface Sci. 158 (1–2) (2010) 2–14.
36. W. Tong, Y. Zhu, Z. Wang, C. Gao, H. Möhwald, Micelles-encapsulated microcap- sules for sequential loading of hydrophobic and water-soluble drugs. Macromol. Rapid Commun. 31 (11) (2010) 1015–1019.
37. R. Palankar, A.G. Skirtach, O. Kreft, M. Bedard, M. Garstka, K. Gould, H. Möhwald, G.B. Sukhorukov, M. Winterhalter, S. Springer, Controlled intracellular release of peptides from microcapsules enhances antigen presentation on MHC class I mol- ecules, Small 5 (19) (2009) 2168–2176.
38. M. Bedard, D. Braun, G.B. Sukhorukov, A.G. Skirtach, Toward self-assembly of nanoparticles on polymeric microshells: near-IR release and permeability, ACS Nano 2 (9) (2008) 1807–1816.
39. T. Borodina, E. Markvicheva, S. Kunizhev, H. Möhwald, G.B. Sukhorukov, O. Kreft, Controlled release of DNA from self-degrading microcapsules, Macromol. Rapid Commun. 28 (18–19) (2007) 1894–1899.
40. K. Köhler, G.B. Sukhorukov, Heat treatment of polyelectrolyte multilayer cap- sules: a versatile method for encapsulation, Adv. Funct. Mater. 17 (13) (2007) 2053–2061.
41. Kreft, O.; Mu~ noz Javier, A.; Sukhorukov, G. B.; Parak, W. J. Polymer Microcapsules as Mobile Local pH-Sensors. J. Mater. Chem. 2007, 17, 4471–4476.
42. C. Kirchner, A.M. Javier, A.S. Susha, A.L. Rogach, O. Kreft, G.B. Sukhorukov, W.J. Parak, Cytotoxicity of nanoparticle-loaded polymer capsules, Talanta 67 (2005) 486–491.
43. A.G. Skirtach, C. Dejugnat, D. Braun, A.S. Susha, W.J. Parak, H. Möhwald, G.B. Sukhorukov, The role of metal nanoparticles in remote release of encapsulated materials, Nano Lett. 5 (7) (2005) 1371–1377.
44. Sukhorukov, G. B.; Rogach, A. L.; Zebli, B.; Liedl, T.; Skirtach, A. G.; Kö hler, K.; Antipov, A. A.; Gaponik, N.; Susha, A. S.; Winterhalter, M.; et al. Nanoengineered Polymer Capsules: Tools for Detection, Controlled Delivery, and Site- Specific Manipulation. Small 2005, 1, 194–200.
45. D.V. Volodkin, A.I. Petrov, M. Prevot, G.B. Sukhorukov, Matrix polyelectrolyte mi- crocapsules: new system for macromolecule encapsulation, Langmuir 20 (8) (2004) 3398–3406.
46. G.B. Sukhorukov, D.V. Volodkin, A.M. Günther, A.I. Petrov, D.B. Shenoy, H. Möhwald, Porous calcium carbonate microparticles as templates for encapsula- tion of bioactive compounds, J. Mater. Chem. 14 (2004) 2073–2081.
47. N.G. Balabushevitch, G.B. Sukhorukov, N.A. Moroz, D.V. Volodkin, N.I. Larionova, E. Donath, H. Möhwald, Encapsulation of proteins by layer-by-layer adsorption of polyelectrolytes onto protein aggregates: factors regulating the protein release, Biotechnol. Bioeng. 76 (3) (2001) 207–213.
48. L. Dähne, S. Leporatti, E. Donath, H. Möhwald, Fabrication of micro reaction cages with tailored properties, J. Am. Chem. Soc. 123 (23) (2001) 5431–5436.
49. Remon, J. Grooten, B.G. de Geest, Polymeric multilayer capsules delivering biotherapeutics, Adv. Drug Deliv. Rev. 63 (9) (2011) 748–761.
50. S. de Koker, B.G. de Geest, C. Cuvelier, L. Ferdinande, W. Deckers, W.E. Hennink, S. de Smedt, N. Mertens, In vivo cellular uptake, degradation, and biocompatibility of polyelectrolyte microcapsules, Adv. Funct. Mater. 17 (18) (2007) 3754–3763.
51. P. Rivera_Gil, S. de Koker, B.G. de Geest, W.J. Parak, Intracellular processing of proteins mediated by biodegradable polyelectrolyte capsules, Nano Lett. 9 (12) (2009) 4398–4402.
52. C. Priest, A. Quinn, A. Postma, A.N. Zelikin, J. Ralston, F. Caruso, Microfluidic poly- mer multilayer adsorption on liquid crystal droplets for microcapsule synthesis, Lab Chip 8 (12) (2008) 2182–2187.
53. Furdyna, J. K. Diluted Magnetic Semiconductors. J. Appl. Phys. 1988, 64, R29–R64.
54. M. Ochs, [+] Dr. S. Carregal-Romero, [+] Prof. W. J. Parak Fachbereich Physik and WZWM, Philipps Universität Marburg Renthof 7, 35037 Marburg (Germany) E-mail: wolfgang.parak@physik.uni-marburg.de Dr. S. Carregal-Romero [+] Bionand. Severo Ochoa 35, 29590 Mµlaga (Spain) Dr. J. Rejman, Prof. K. Braeckmans, Prof. S. C. De Smedt Laboratory of General Biochemistry and Physical Pharmacy Ghent University Harelbekestraat 72, Ghent (Belgium) Prof. K. Braeckmans Center for Nano and Biophotonics, Ghent University Harelbekestraat 72, Ghent (Belgium) [ + ] These authors contributed equally to this work.
55. J.M. McKiernan, L.J. Barlow, M.A. Laudano, M.J. Mann, D.P. Petrylak, M.C. Benson, A phase I trial of intravesical nanoparticle albumin-bound paclitaxel in the treat- ment of bacillus calmette-guerin refractory nonmuscle invasive bladder cancer. J. Urology 186 (2) (2011) 448–451.
56. J. Han, A. Loudet, R. Barhoumi, R.C. Burghardt, K. Burgess, A ratiometric pH report- er for imaging protein-dye conjugates in living cells, J. Am. Chem. Soc. 131 (5) (2009) 1642–1643.
57. X. Zhang, M. Oulad-Abdelghani, A.N. Zelkin, Y.J. Wang, Y. Haikel, D. Mainard, J.C. Voegel, F. Caruso, N. Benkirane-Jessel, Poly(L-lysine) nanostructured particles for gene delivery and hormone stimulation, Biomaterials 31 (7) (2010) 1699–1706.
58. V.R. Sinha, A. Trehan, Biodegradable microspheres for protein delivery, J. Control. Release 90 (3) (2003) 261–280.
59. R.F. Murphy, S. Powers, C.R. Cantor, endosome pH measured in single cells by dual fluorescence flow cytometry: rapid acidification of insulin to pH 6, J. Cell Biol. 98 (5) (1984) 1757–1762.
60. B.V. Enustun, J. Turkevich, Coagulation of colloidal gold, J. Am. Chem. Soc. 85 (21) (1963) 3317–3328.
61. N. Bhatia, G. von Maltzahn, J.H. Park, A. Agrawal, N.K. Bandaru, S.K. Das, M.J. Sailor, Computationally guided photothermal tumor therapy using long- circulating gold nanorod antennas, Cancer Res. 69 (9) (2009) 3892–3900.
62. Emiliani, V.; Sanvitto, D.; Tramier, M.; Piolot, T.; Petrasek, Z.; Kemnitz, K.; Durieux, C.; Coppey-Moisan, M. Low-Intensity Two-Dimensional Imaging of Fluorescence Lifetimes in Living Cells. Appl. Phys. Lett. 2003, 83, 2471–2473.
63. Um, S. H.; Lee, J. B.; Kwon, S. Y.; Li, Y.; Luo, D. Dendrimer-like DNA-Based Fluorescence Nanobarcodes. Nat. Protoc. 2006, 1,995–1000.
64. Lin, C.-A. J.; Sperling, R. A.; Li, J. K.; Yang, T.-Y.; Li, P.-Y.; Zanella, M.; Chang, W. H.; Parak, W. J. Design of an Amphiphilic Polymer for Nanoparticle Coating and Func- tionalization. Small 2008, 4, 334–341. REFERENCES AND NOTES 1. Buckler, K. J.; Vaughanjones, R. D. Application of a New pH-Sensitive Fluoroprobe (Carboxy-Snarf-1) for Intracellular pH Measurement in Small, Isolated Cells. Pflug. Arch. Eur.
65. Archer, P. I.; Santangelo, S. A.; Gamelin, D. R. Direct Observation of spd Exchange Interactions in Colloidal Mn 2 -and Co 2 -Doped CdSe Quantum Dots. Nano Lett. 2007, 7, 1037–1043.
66. E.B. Dickerson, E.C. Dreaden, X. Huang, I.H. El-Sayed, H. Chu, S. Pushpanketh, J.F. McDonald, M.A. El-Sayed, Gold nanorod assisted near-infrared plasmonic photo- thermal therapy (PPTT) of squamous cell carcinoma in mice, Cancer Lett. 269 (1) (2008) 57–66.
67. Decher, G. Fuzzy Nanoassemblies: Toward Layered Poly- meric Multicomposites. Science 1997, 277, 1232–1237.
68. R.A. Alvarez-Puebla, A. Agarwal, P. Manna, B.P. Khanal, P. Aldeanueva-Potel, E. Carbo-Argibay, N. Pazos-Perez, L. Vigderman, E.R. Zubarev, N.A. Kotov, L.M. Liz- Marzan, Gold nanorods 3D-supercrystals as surface enhanced Raman scattering spectroscopy substrates for the rapid detection of scrambled prions, Proc. Natl. Acad. Sci. U. S. A. 108 (20) (2011) 8157–8161.
69. A.R. Lowery, A.M. Gobin, E.S. Day, N.J. Halas, J.L. West, Immunonanoshell laser- assisted therapy targets and ablates tumor cells, Breast Cancer Res. Treat. 100 (2006) S289–S.
70. Sheng, W.; Kim, S.; Lee, J.; Kim, S. W.; Jensen, K.; Bawendi, M. G. In-Situ Encapsulation of Quantum Dots into Polymer Microspheres. Langmuir 2006, 22, 3782–3790.
71. Chan, W. C. W.; Maxwell, D. J.; Gao, X.; Bailey, R. E.; Han, M.; Nie, S. Luminescent Quantum Dots for Multiplexed Biolo- gical Detection and Imaging. Curr. Opin. Biotechnol. 2002, 13,40–46.
72. Sukhorukov, G. B.; Donath, E.; Davis, S.; Lichtenfeld, H.; Caruso, F.; Popov, V. I.; Mö hwald, H. Stepwise Polyelectrolyte Assembly on Particle Surfaces: A Novel Approach to Colloid Design. Polym. Adv. Technol. 1998, 9, 759–767.
73. N.O. Dhoot, M.A. Wheatley, Microencapsulated liposomes in controlled drug delivery: strategies to modulate drug release and eliminate the burst effect, J. Pharm. Sci. 92 (3) (2003) 679–689.
74. J. Cui, Y. Wang, A. Postma, J. Hao, L. Hosta-Rigau, F. Caruso, Monodisperse polymer capsules: tailoring size, shell thickness, and hydrophobic cargo loading via emulsion templating. Adv. Funct. Mater. 20 (10) (2010) 1625–1631.
75. Li, Y. G.; Cu, Y. T. H.; Luo, D. Multiplexed Detection of Pathogen DNA with DNA-Based Fluorescence Nanobar- codes. Nat. Biotechnol. 2005, 23, 885–889.
76. Goldman, E. R.; Clapp, A. R.; Anderson, G. P.; Uyeda, H. T.; Mauro, J. M.; Medintz, I. L.; Mattoussi, H. Multiplexed Toxin Analysis Using Four Colors of Quantum Dot Fluororeagents. Anal. Chem. 2004, 76, 684–688.
77. Duchesne, T. A.; Brown, J. Q.; Guice, K. B.; Nayak, S. R.; Lvov, Y. M.; McShane, M. J.; Priezzhev, A. V.; Cote, G. L. Nanoassembled Fluorescent Microshells as Biochemical Sensors. Proc. SPIE 2002, 4624, 66–75.
78. Donath, E.; Sukhorukov, G. B.; Caruso, F.; Davis, S. A.; Möhwald, H. Novel Hollow Polymer Shells by Colloid- Templated Assembly of Polyelectrolytes. Angew.Chem., Int. Ed. 1998, 37, 2202–2205.
79. B. Radt, T.A. Smith, F. Caruso, Optically addressable annostructured capsules, Adv. Mater. 16 (23–24) (2004) 2184–2189.
80. Clark, H. A.; Hoyer, M.; Philbert, M. A.; Kopelman, R. Optical Nanosensors for Chemical Analysis inside Single Living Cells. 1. Fabrication, Characterization, and Methods for Intracellular Delivery of PEBBLE Sensors. Anal. Chem. 1999, 71, 4831–4836.
81. A. Muñoz_Javier, P. del Pino, M. Bedard, A.G. Skirtach, D. Ho, G. Sukhorukov, C. Plank, W.J. Parak, Photoactivated release of cargo from the cavity of polyelectro- lye capsules to the cytosol of cells, Langmuir 24 (2009) 12517–12520.
82. D.P. O'Neal, L.R. Hirsch, N.J. Halas, J.D. Payne, J.L. West, Photo-thermal tumor ab- lation in mice using near infrared-absorbing nanoparticles, Cancer Lett. 209 (2) (2004) 171–176.
83. Volodkin, D. V.; Larionova, N. I.; Sukhorukov, G. B. Protein Encapsulation via Porous CaCO 3
84. Gao, X.; Nie, S. Quantum Dot- Encoded Beads. In NanoBiotechnology Protocols; Rosenthal, S. J., Wright, D. W., Eds.; Humana Press: Totowa, NJ, 2005; pp 6171.
85. Alivisatos, A.; Gu, W.; Larabell, C. Quantum Dots as Cellular Probes. Annu. Rev. Biomed. Eng. 2005, 7,55–76.
86. Han, M.; Gao, X.; Su, J. Z.; Nie, S. Quantum-Dot-Tagged Microbeads for Multiplexed Optical Coding of Biomole- cules. Nat. Biotechnol. 2001, 19, 631–635.
87. Jezek, P.; Mahdi, F.; Garlid, K. D. Reconstitution of the Beef-Heart and Rat-Liver Mitochondrial K /H (Na /H ) AntiporterOQuantitation of K Transport with the Novel Fluorescent-Probe, PBFI. J. Biol. Chem. 1990, 265, 10522–10526.
88. Nath, S.; Jezek, P.; Garlid, K. D. Reconstitution of the Na -Selective Na /H Antiporter from Beef- Heart MitochondriaOQuantitation of Na Transport With The Novel Fluorescent-Probe, SBFI. Biophys. J. 1990, 57, A477.
89. Kasner, S. E.; Ganz, M. B. Regulation of Intracellular Potassium in Mesangial CellsOA Fluorescence Analysis Using the Dye, PBFI. Am. J. Physiol. 1992, 262, F462–F467.
90. N. Antipina Maria, G.B. Sukhorukov, Remote control over guidance and release properties of composite polyelectrolyte based capsules, Adv. Drug Deliv. Rev. 63 (9) (2011) 716–729.
91. del Mercato, L. L.; Abbasi, A. Z.; Parak, W. J. Synthesis and Characterization of Ratiometric Ion-Sensitive Polyelectro- lyte Capsules. Small 2011, 7, 351–363.
92. L.E. Bromberg, E.S. Ron, Temperature-responsive gels and thermogelling polymer matrixes for protein and peptide delivery, Adv. Drug Deliv. Rev. 31 (3) (1998) 197–221.
93. I.M. Abdulagatov, U.B. Magomedov, Thermal conductivity of aqueous solutions of Nacl and Kcl at high pressures, Int. J. Thermophys. 15 (3) (1994) 401–413.
94. Dahan, M.; Laurence, T.; Pinaud, F.; Chemla, D. S.; Alivisatos, A. P.; Sauer, M.; Weiss, S. Time-Gated Biological Imaging by use of Colloidal Quantum Dots. Opt. Lett. 2001, 26, 825–827.
95. P. Moulin, H. Roques, Zeta potential measurement of calcium carbonate, J. Colloid Interface Sci. 261 (1) (2003) 115–126.
96. L.C.d.L. Novaes, P.G. Mazzola, A. Pessoa, Jr., T.C.V. Penna, Citrate and phosphate in- fluence on green fluorescent protein thermal stability. Biotechnol. Prog. 27 (1) (2010) 269–272.
97. W.R. Gombotz, D.K. Pettit, Biodegradable polymers for protein and peptide drug delivery, Bioconjug. Chem. 6 (4) (1995) 332–351.
98. A.S. Angelatos, B. Radt, F. Caruso, Light-responsive polyelectrolyte/gold nanopar- ticle microcapsules, J. Phys. Chem. B 109 (2005) 3071–3076.
99. S.K. Dondapati, T.K. Sau, C. Hrelescu, T.A. Klar, F.D. Stefani, J. Feldmann, Label-free biosensing based on single gold nanostars as plasmonic transducers, ACS Nano 4 (11) (2010) 6318–6322.
100. Ruedas-Rama, M. J.; Wang, X.; Hall, E. A. A Multi-ion Particle Sensor. Chem. Commun. (Cambridge) 2007, 1544–1546.
101. Z. Krpetic, P. Nativo, V. See, I.A. Prior, M. Brust, M. Volk, Inflicting controlled non- thermal damage to subcellular structures by laser-activated gold nanoparticles, Nano Lett. 10 (11) (2010) 4549–4554.
102. G. Han, P. Ghosh, V.M. Rotello, Multi-functional gold nanoparticles for drug delivery, Adv. Exp. Med. Biol. 620 (2007) 48–56.
103. Graefe, A.; Stanca, S. E.; Nietzsche, S.; Kubicova, L.; Beckert, R.; Biskup, C.; Mohr, G. J. Development and Critical Evaluation of Fluorescent Chloride Nanosensors. Anal. Chem. 2008, 80, 6526–6531.
104. Meuwis, K.; Boens, N.; De Schryver, F. C.; Gallay, J.; Vincent, M. Photophysics of the Fluorescent K þ Indicator PBFI. Biophys. J. 1995, 68, 2469–2473.
105. R. Bardhan, S. Lal, A. Joshi, N.J. Halas, Theranostic nanoshells: from probe design to imaging and treatment of cancer, Acc. Chem. Res. 44 (10) (2011) 936–946.
106. Buck, S. M.; Koo, Y. L.; Park, E.; Xu, H.; Philbert, M. A.; Brausel, M. A.; Kopelman, R. Optochemical Nanosensor Pebbles: Photonic Explorers for Bioanalysis with Biologically Loca- lized Embedding. Curr. Opin. Chem. Biol. 2004, 8, 540–546.
107. Erwin, S. C.; Zu, L. J.; Haftel, M. I.; Efros, A. L.; Kennedy, T. A.; Norris, D. J. Doping Semiconductor Nanocrystals. Nature 2005, 436, 91– 94.

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