Liposomes for DNA Nanotechnology: Preparation, Properties, and Applications - DNA Nanotechnology: From Structure to Function - page 71

variations. Many of these disadvantages can be overcome by using aptamers
[ 62 , 63 ]. Lu et al. reported cisplatin-encapsulated liposomes with functionalized
aptamers for cancer-cell-specific targeting. In addition they demonstrated a method
to turn off the drug delivery via cDNA [ 64 ]. A 26-mer DNA aptamer with a
cholesterol modification was used with a high binding affinity for nucleolin (NCL).
The overexpression of NCL in cell membranes has been linked to many cancers
including breast cancer. The targeted liposomes showed an increase in cell death,
whereas addition of cDNA resulted in almost full cell viability. Their system clearly
demonstrated the combination of aptamer and liposome for effective treatment.
In another system, Kang et al. linked an sgc8 aptamer specific for leukemia
cells to a liposome [ 65 ]. The aptamer was modified with a fluorophore, and the
liposome contained another fluorophore to monitor both receptor binding and
content delivery. The specificity of sgc8 aptamer allowed for cell-specific delivery.
Mann et al. modified a liposome with an aptamer targeting E-selection that is
expressed in tumor vasculature [ 66 ]. They studied intravenous administration of this
system encapsulated with rhodamine dye and found accumulation at the tumor site
without decreasing the circulation half-life of the system. These studies demonstrate
the feasibility of aptamer-functionalized liposomes for cancer therapy.

4.10 Summary and Future Directions

In summary, significant progress has been made in the past decade or so on DNA-
functionalized liposomes. Thanks to the advance of technology, arbitrary DNA
sequences with many types of modifications are readily available. At the same
time, many types of lipids can be purchased in high purity. Many new biosensors,
model biophysical systems, and drug delivery vehicles have been prepared using
DNA-functionalized liposomes. However, our fundamental understanding on the
membrane biophysics is still quite limited, and many features in the cell mem-
brane have not been harnessed. For example, we can envision smart systems by
incorporating artificial ion channels to better gate the communication between the
internal and external regions of the bilayer. For biomedical applications, using
aptamer-functionalized liposomes for in vivo delivery need to be studied in more
detail. For fundamental biophysical studies, DNA will continue to play a role
in understand liposome fusion, fission, lateral diffusion, and multivalent ligand
binding. For example, if liposome fusion can be precisely controlled, we can control
chemical reactions in such nanoscale containers.

References

1. Seeman NC (2003) DNA in a material world. Nature 421:427-431
2. Pinheiro AV, Han D, Shih WM, Yan H (2011) Challenges and opportunities for structural DNA
nanotechnology. Nat Nanotechnol 6:763-772