Chemistry Reference
In-Depth Information
Amphiphilic block copolymers capable of binding to DNA can be used as
nonviral delivery vehicles, as mentioned above (Cleek et al. 1997; Jeong and Park
2001). For efficient DNA delivery, the vehicle should have the necessary recognition
and encapsulation capabilities. Toward this goal, a block copolymer having biode-
gradable poly(
D
,
L
-lactic-co-glycolic acid) (PLGA) as one block and an oligodinucleo-
tide (ODN, CACGTTGAGGGGCAT) as the other block was synthesized. It is
expected that the ODN/PLGA conjugate can be more efficiently delivered into the
cells by an endocytosis mechanism, in contrast to ODN itself that is transported
across the cell membrane by passive diffusion. The ODN/PLGA micelles released
ODN in a sustained manner because of the controlled degradation of PLGA.
In addition to utilizing natural ODNs in block copolymers, ODN mimics have also
been studied using polymers with the capability of forming hydrogen bonds. Bazzi
and colleagues (Bazzi and Sleiman 2002; Bazzi et al. 2003) have reported diblock
and triblock amphiphilic polymers with diamidopyridine (DAP) and dicarboximide
moieties as molecular recognition units and studied their micelle formation properties
(Chart 2.4).
They found the formation of
40-nm particles in a polymer, where two recogniz-
ing blocks are separated by a neutral linker. The demonstration of disassembly is as
interesting as assembly formation, because the ease of disassembly is the greatest
advantage of noncovalent assemblies. One could imagine how this could be particu-
larly useful in utilizing these types of assemblies as delivery vehicles. Toward this
goal, Bazzi and coworkers (Bazzi and Sleiman 2002; Bazzi et al. 2003) synthesized
a diblock copolymer containing DAP and a hydrophobic block, which forms
190-nm aggregates in CHCl
3
. The aggregation is possibly due to hydrogen
bonding between DAP units, which are weakly self-complementary. This weak inter-
action was proven by the addition of maleimide, which binds more strongly with
DAP. This disrupts the hydrogen bonding between DAP units that results in disas-
sembling the micelle. To further prove that micelle disassembly is a result of the
specific interaction between maleimide and DAP, N-methylmaleimide was added
to the micellar solution. N-Methylmaleimide has similar structural features to malei-
mide, except that it does not associate with DAP. The micelle solution remained
turbid even after boiling with N-methylmaleimide, confirming that the micelle did
not disassemble. However, the micelles were disassembled upon the addition of
succinimide, N-butylthymine, and N-hexylthymine.
Similarly, small triblock copolymer 7 containing DAP and thymine (THY) as
outer blocks (Chart 2.4) was assembled to form a micelle because of the noncovalent
interaction between DAP and THY. These micelles were shown to disassemble upon
the addition of THY containing small molecules. The micelles could be efficiently
disassembled by small molecule guests, albeit with less selectivity. This is possibly
because of the weak interaction between the DAP units. To bring more selectivity,
Bazzi and cohorts (Bazzi and Sleiman 2002; Bazzi et al. 2003) synthesized a triblock
copolymer containing DAP and THY blocks, which were separated by a hydrophobic
block. This polymer formed large micellar aggregates. Because of the strong inter-
action between DAP and THY, these assemblies were not disassembled by many
guest molecules, confirming the strong hydrogen bonding between the DAP and
