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pH Sensitive Fluorescent-Magnetic Nanocomposites for Intracellular Detection and Manipulation

Dhananjay Thakur1, Lee Siers2, Thierno Baldet2, and Jessica O. Winter3. (1) Biophysics Program, the Ohio State University, 140 W 19th Ave, Columbus, OH 43210, (2) Chemical and Biomolecular Engineering, the Ohio State University, 140 W19th Ave, Columbus, OH 43210, (3) Chemical and Biomolecular Engineering/Biomedical Engineering/ Biophysics Program, Ohio State Unversity, 140 W 19th Ave, Columbus, OH 43210

Hybrid nanoparticles have multimodal applications in biology and medicine. Fluorescent magnetic nanoparticles could be used for mechanical manipulation of cells and subcellular features with real time monitoring, while simultaneously taking advantage of the variation of fluorescence with changes in the physical structure and local environment of the nanoparticles. Although, current high temperature synthesis methods using organic solvents produce nanoparticles with better surface passivation and particle stability than aqueous methods, the aqueous route can produce particles with interesting physical properties while retaining relative simplicity in procedure. We have attempted to synthesize fluorescent - magnetic nanocomposites by using a bifunctional linker molecule to bind quantum dots and superparamagnetic iron oxide nano-particles. Cadmium sulfide nanocrystals were synthesized through arrested precipitation using known methods [1,2] and were linked to iron oxide nanoparticles using a bifunctional ligand (MPS - 3-mercaptopropyl trimethoxy silane).

Water soluble fluorescent magnetic particles were obtained in an aqueous solution at a pH below 2.0. The particles remained stable in solution for up to 48 hrs, after which aggregates were formed that precipitated out of the solution. The fluorescence intensity showed a strong dependence on the pH of the local environment, while the magnetic properties were unaffected. Quenching of fluorescence was observed at a neutral pH. Particles formed large aggregates and precipitated almost immediately. Fluorescence intensity increased rapidly as pH was reduced, with a peak intensity at pH below 2.0. The fluorescence peak was recovered after recycling of pH in the range 1.5 to 7.5. We are currently working on stabilizing the particles across the pH range required for physiological applications and characterizing them on the basis of initial particle size, ligand concentration and temperature during synthesis. This pH dependence could be harnessed for selective targeting and identification of subcellular environments and cellular processes such as endocytosis, exocytosis and changes in the proton flux during oxidative phosphorylation.

1.Winter J. O, Gatzert S., Korgel B.A., Schmidt C.E. (2005). Variation of Cadmium Sulfide Nanoparticles Size with Altered Aqueous Synthesis Conditions. Colloids and Surfaces A, 254(1-3): 147-157

2.Chen H.M., Huang X.F., Xu L., Xu J., Chen K.J., Feng D., Superlattices Microstruct., Volume: 27, (2000), p. 1