doxorubicin into HeLa cells. Cytotoxicity assay showed an enhanced bioactivity of
doxorubicin compared to free prodrug. In their follow-up work, CB[7] was used in
the self-assembly of MOP for multistimuli-responsive release of dye or drug from
hydrophobic phase [35]. In their design, CB[7] was covalently conjugated to MOP
backbone. Guest moiety with hydrophobic alkyl chain was incorporated into MOP
hydrophobic phase, which could be encapsulated by CB[7] as gatekeeper for
encapsulated cargo. Dye or doxorubicin was loaded into hydrophobic layer of
MOP self-assembly. This MOP self-assembly was responsive to multiple stimuli
types. By adding competitive guest adamantane amine or applying photo-irradiation
to trigger the trans-to-cis conversion of azobenzene, MOP self-assembly could swell
to release encapsulated cargo. The work based on MOP is a good example for selfassembly systems based on both coordination interaction and host-guest chemistry
for drug delivery purposes. The interplay of both interactions renders it possible to
control the release of cargo.
Mesoporous silica is an important type of inorganic nanomaterials, which could
be used to encapsulate drug and dye in its porous channels. Macrocyclic host
molecules have been used as “nanovalves” to control the open and close of channels,
which renders the stable encapsulation and controlled release of cargo. One of the
interesting applications is to design “logic gate” based on nanovalve [36]. As shown
in Fig. 17, Angelos et al. reported the use of CB[6] to control mesoporous silica
channels. The surface of mesoporous silica nanoparticles (MSN) was modified by
pH-responsive guest. The interior of nanoparticle channel was functionalized by
photo-responsive azobenzene moiety. Cargo was loaded into MSN channels. Four
hundred forty-eight nm light and base were used as two types of inputs. It was
discovered that cargo release could only be achieved when both inputs were
employed. Therefore, this system was AND logic gate. MSN-based logic gate
could be used to control the release of cargo responding to two stimuli types.
Because more than one type of stimuli may exist in pathological tissues, this AND
logic gate may have interesting application for sophisticated drug delivery. This
design may also be applied in computing science.
Díez et al. reported a MSN-based logic gate responsive to enzymatic stimuli
[37]. Two enzymes, esterase and glucose oxidase, were conjugated to Au nanoparticles,
which subsequently complexed with MSN to form Janus nanoparticles (Fig. 18).
MSN was loaded with Ru-complex as model cargo. The nanovalve was controlled
by pH-responsive host-guest interaction between CD and 1-propyl-1H-benzimidazole guest. The resulting nanodevice could respond to two inputs, ethyl butyrate
and D-glucose. Catalyzed by enzymes, ethyl butyrate would produce butyric acid,
and D-glucose would generate gluconic acid. Both biocatalytic reactions resulted in
a drop in pH and the protonation of guest. The overall effect was the removal of CD
gatekeeper and release of cargo. This nanodevice was discovered to be OR logic
gate: the addition of either ethyl butyrate or D-glucose would result in cargo release.
Nanodevice was tested in living cells using doxorubicin as cargo. OR logic gate was
confirmed in vitro with both fluorescence and cell viability observations. It is a
common practice to convert enzymatic stimuli to chemical stimuli to achieve cargo
release in drug delivery and tissue engineering. This work is an example for this type
23 Stimuli-Responsive Self-Assembly Based on Macrocyclic Hosts and Biomedical. . .
627
doxorubicin compared to free prodrug. In their follow-up work, CB[7] was used in
the self-assembly of MOP for multistimuli-responsive release of dye or drug from
hydrophobic phase [35]. In their design, CB[7] was covalently conjugated to MOP
backbone. Guest moiety with hydrophobic alkyl chain was incorporated into MOP
hydrophobic phase, which could be encapsulated by CB[7] as gatekeeper for
encapsulated cargo. Dye or doxorubicin was loaded into hydrophobic layer of
MOP self-assembly. This MOP self-assembly was responsive to multiple stimuli
types. By adding competitive guest adamantane amine or applying photo-irradiation
to trigger the trans-to-cis conversion of azobenzene, MOP self-assembly could swell
to release encapsulated cargo. The work based on MOP is a good example for selfassembly systems based on both coordination interaction and host-guest chemistry
for drug delivery purposes. The interplay of both interactions renders it possible to
control the release of cargo.
Mesoporous silica is an important type of inorganic nanomaterials, which could
be used to encapsulate drug and dye in its porous channels. Macrocyclic host
molecules have been used as “nanovalves” to control the open and close of channels,
which renders the stable encapsulation and controlled release of cargo. One of the
interesting applications is to design “logic gate” based on nanovalve [36]. As shown
in Fig. 17, Angelos et al. reported the use of CB[6] to control mesoporous silica
channels. The surface of mesoporous silica nanoparticles (MSN) was modified by
pH-responsive guest. The interior of nanoparticle channel was functionalized by
photo-responsive azobenzene moiety. Cargo was loaded into MSN channels. Four
hundred forty-eight nm light and base were used as two types of inputs. It was
discovered that cargo release could only be achieved when both inputs were
employed. Therefore, this system was AND logic gate. MSN-based logic gate
could be used to control the release of cargo responding to two stimuli types.
Because more than one type of stimuli may exist in pathological tissues, this AND
logic gate may have interesting application for sophisticated drug delivery. This
design may also be applied in computing science.
Díez et al. reported a MSN-based logic gate responsive to enzymatic stimuli
[37]. Two enzymes, esterase and glucose oxidase, were conjugated to Au nanoparticles,
which subsequently complexed with MSN to form Janus nanoparticles (Fig. 18).
MSN was loaded with Ru-complex as model cargo. The nanovalve was controlled
by pH-responsive host-guest interaction between CD and 1-propyl-1H-benzimidazole guest. The resulting nanodevice could respond to two inputs, ethyl butyrate
and D-glucose. Catalyzed by enzymes, ethyl butyrate would produce butyric acid,
and D-glucose would generate gluconic acid. Both biocatalytic reactions resulted in
a drop in pH and the protonation of guest. The overall effect was the removal of CD
gatekeeper and release of cargo. This nanodevice was discovered to be OR logic
gate: the addition of either ethyl butyrate or D-glucose would result in cargo release.
Nanodevice was tested in living cells using doxorubicin as cargo. OR logic gate was
confirmed in vitro with both fluorescence and cell viability observations. It is a
common practice to convert enzymatic stimuli to chemical stimuli to achieve cargo
release in drug delivery and tissue engineering. This work is an example for this type
23 Stimuli-Responsive Self-Assembly Based on Macrocyclic Hosts and Biomedical. . .
627