Biomedical Engineering Reference
In-Depth Information
(GaAs, GaN, InP and InAs), which are 'overcoated' with a layer of ZnS (Sanvicens
and Marco 2008 ). Quantum dots are photostable and resistant to photobleaching,
and they show size- and composition-tunable emission spectra and high quantum
yield, as well as exceptional resistance to photo and chemical degradation. The
unique optical properties of QDs make them appealing as in vivo and in vitro fluo-
rophores in a variety of biological investigations, in which traditional fluorescent
labels based on organic molecules fall short of providing long-term stability and
simultaneous detection of multiple signals (Medintz et al. 2005 ).
Burgess et al. first showed that quantum dots could be covalently conjugated to
pDNA for transfection and long-term intracellular and intranuclear tracking
(Srinivasan et al. 2006 ). Conjugation of pDNA with phospholipid-coated QDs was
achieved using a peptide nucleic acid (PNA)-N-succinimidyl-3-(2-pyridylthio) pro-
pionate linker. AFM imaging revealed that multiple QDs were attached in a cluster
at the PNA-reactive site of the pDNA. These QD-DNA conjugates could express the
reporter protein in Chinese hamster ovary (CHO-K1) cells with an efficiency of ca.
62%, which was comparable to the control (unconjugated) pDNA. In addition, con-
focal imaging could be employed to study the intracellular trafficking and distribu-
tion of QD-DNA conjugates, utilizing the inherent fluorescence possessed by QDs.
Nie and Gao et al. developed multifunctional nanoparticles for siRNA delivery and
imaging based on QDs and proton-sponging polymer coating (Yezhelyev et al.
2008 ). Transfection studies showed dramatic improvement in gene silencing effi-
ciency by 10~20-fold, when compared with commercial transfection agents (TransIT
and JetPEI) in MDA-MB-231 cells. These QD-siRNA nanoparticles are also dual-
modality optical and electron-microscopy probes, allowing real-time tracking and
ultrastructural localization of QDs during delivery and transfection. Most recently,
siRNA conjugated QDs have been fabricated as a multifunctional nanoplatform to
deliver siRNA and to elucidate the EGFRvIII-knockdown effect of PI3K signaling
pathway in U87-EGFRvIII (Jung et al. 2010 ). Two different strategies were devel-
oped for the siRNA-QD conjugates: (1) siRNA and QDs were coupled through
disulfide linkage to release the siRNA upon entering the cells by cleavage of the
disulfide linkage, through enzymatic reduction or ligand exchange (e.g. glutathi-
one); and (2) siRNA and QDs were conjugated using a robust linker (3-maleimido-
propionic acid pentafluorophenyl ester) which enabled the tracking of siRNA-QDs
within the cells. In addition to selective inhibition of human brain tumor cells, real-
time monitoring of down-regulated signaling pathway could also be implemented.
6.3
Gold Nanorods as Multifunctional Carriers
Multifunctional nanorods offer a unique capability to combing a number of essen-
tial diagnostic, imaging, delivery and dosage properties. In addition, their proper-
ties have been designed and explored for specific biomedical applications by taking
advantage of the additional degrees of freedom associated with nanorods in com-
parison to spherical particles (Pearce et al. 2007 ).
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