Liposomes for DNA Nanotechnology: Preparation, Properties, and Applications - DNA Nanotechnology: From Structure to Function - page 56

only for complementary nucleic acids but also for a diverse range of metal ions,
small molecules, and proteins. Such binding DNAs are referred to as aptamers [ 3 ].
Coupling DNA with the optical, magnetic, electric, and catalytic properties
of various inorganic nanomaterials has found use in a number of applications
for analytical chemistry, imaging, drug delivery, and materials science [ 4 - 8 ].
Liposomes are composed of two stacked layers of lipids forming a closed shell;
this lipid bilayer also composes the basic structural component of cell membranes.
For this reason, liposomes have been commonly used as a model to study the cell
membrane. In recent years, it has been found that lipid bilayers also possess very
rich biophysical features such as fluidity and raft formation important for cellular
signaling and transport. Although most liposomes do not possess interesting optical
and electronic properties, compared to inorganic nanoparticles, liposomes have a
number of other interesting features. For example, liposomes are soft and can be
easily deformed by weak intermolecular forces while most inorganic nanoparticles
cannot. Since liposomes are made up of self-assembled lipids, associated DNA or
other ligands are mobile and can diffuse laterally within the liposome, while ligands
attached to inorganic particles are fixed. The surface charge, lateral diffusivity, and
size of liposomes can be quantitatively controlled by tuning lipid formulation and
preparation method. In addition, liposomes can undergo complex reactions such
as fusion and fission that are usually difficult to achieve with inorganic particles.
The internal compartment of liposomes can encapsulate concentrated fluorophores
and drugs, allowing for signal amplification and controlled release. For example,
liposome permeability can be controlled by temperature or adding surfactants.
Finally, most liposomes are nontoxic and have excellent biocompatibility, which
has popularized their use in drug delivery applications.
Studying DNA-functionalized liposomes is motivated by several factors. First,
from a biophysical perspective, the cell membrane is associated with various
proteins, allowing complex processes such as membrane fusion to take place. While
various fusion proteins and peptides have been identified, it remains difficult to have
a molecular-level understanding of membrane fusion. Although DNA is not part of
the natural cell membrane structure, the programmability of DNA hybridization
can help us better understand and control liposome fusion and other membrane
processes. Second, new physical principles may be elucidated by comparing soft
liposomes with hard inorganic nanoparticles, where interparticle distance can be
precisely controlled by DNA. Last, molecular recognition and targeting properties
of DNA alone can be used for making biosensors, and liposomes are ideal for
signal amplification and drug containment. Therefore, a combination of DNA and
liposomes would allow potential for new applications in sensing and drug delivery.
In the past 10 years, DNA-functionalized liposomes have emerged as a new platform
for nanotechnology. In this chapter, we focus on the preparation of DNA-liposome
conjugates, their respective biophysical properties, and related applications. Using
cationic liposomes to condense nucleic acids for gene transfection has been
practiced for many years. Many excellent review papers have been published on
this subject [ 9 , 10 ], which will not be covered here.