One goal of nanotechnology is to prepare cellular nanoprobes for various biological applications where conventional molecular probes fall short of long-term stability and simultaneous detection of multiple signals. Successful development of cellular nanoprobes requires the availability of a library of functional nanoparticles, knowledge of their interactions with cells and mechanism of cellular entry and to modulate these interactions by appropriate design of surface functionality. Although a great deal of research has been done in past 15 years, only limited success has been achieved in live cell labeling with high specificity, sub-cellular targeting and single molecule trafficking. This article focuses on the author's effort in making cellular imaging nanoprobes from different nanoparticles and discusses the most critical issues in the context of current knowledge, such as different variables that often influence labeling, non-specific binding/uptake of nanoprobes and specific live cell labeling. Finally, the important role of coating chemistry to overcome these problems has been highlighted and some successful labeling results have been summarized.
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