2 February 2012 Further progress in cytosolic cellular delivery of quantum dots
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Abstract
Currently there is considerable interest in using bioconjugated nanoparticles for in vivo imaging, biosensing and theranostics. Luminescent CdSe/ZnS core shell semiconductor quantum dots (QDs) have unique optical properties and bioconjugation capabilities that make them ideal prototypes for these purposes. We have previously described the metal-affinity association between the imidazole groups of terminal hexahistidine residues of peptides and proteins and the ZnS shell of quantum dots as a useful bioconjugation technique. We have also demonstrated that QDs labeled with an oligohistidine-tagged cell penetrating peptide (CPP) derived from the HIV TAT-protein could undergo specific endocytosis-mediated cellular uptake in both HEK293T/17 and COS-1 cells. However, the QDs were predominantly sequestered in the endosomes. This remains a significant hindrance to future potential cellular imaging applications which require the QDs to access other subcellular organelles. Here we describe the testing of several cytosolic QD delivery modalities including microinjection, the commercial cytosolic delivery agent PULSin, and the cytosolic delivery peptide Palm-1. Palm-1, a palmitylated peptide that is capable of both cellular uptake and rapid endosomal escape in multiple cell lines without concomitant toxicity, is shown to be the superior method for cytosolic delivery of QDs. Potential intracellular applications for this peptide are discussed.
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Kelly Boeneman Gemmill, Kelly Boeneman Gemmill, James B. Delehanty, James B. Delehanty, Michael H. Stewart, Michael H. Stewart, Kimihiro Susumu, Kimihiro Susumu, Juan B. Blanco-Canosa, Juan B. Blanco-Canosa, Philip E. Dawson, Philip E. Dawson, Alan Huston, Alan Huston, Igor Medintz, Igor Medintz, } "Further progress in cytosolic cellular delivery of quantum dots", Proc. SPIE 8232, Colloidal Nanocrystals for Biomedical Applications VII, 82320B (2 February 2012); doi: 10.1117/12.906801; https://doi.org/10.1117/12.906801
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