Abstract
Quantum dots (QDs) are engineered nanoparticles (NP) that have shown great promise with potential for a plethora of biological and biomedical applications, such as drug delivery/activation and cellular imaging. However, the physicochemical characteristics of QDs are very different from conventional fluorophores. As such, cytosolic delivery of bioconjugates QDs into live cells has remained challenging. We sought to develop a fluorescent nanoparticle vehicle that could efficiently deliver small molecule drugs to target lymphocyte populations while enabling direct single-particle visualization. The dentin phosphophoryn draws our attention because it is nature's most acidic protein found predominantly in the dentin extracellular matrix. Its unique amino acid composition containing Asp-Ser (DS)-rich repeats makes it highly anionic. QDs conjugated with repetitive DSS-rich domains(DSS-QD) exhibited membrane-penetrating activity in T cells. We demonstrate highly efficient delivery of QDs into live cell cytoplasm directly while the QDs remained mobile in nonaggregated states. The ability to deliver and track QDs may invite unconventional strategies for studying biological processes and biophysical properties in living cells with spatial and temporal precision, one nanoparticle at a time.
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