4 Aptamer-Based Drug Delivery Systems
91
in vivo, with great potential in designing similar platforms to silent other diseaserelated genes. For an enhanced cellular uptake, Seleci et al. [72] combined cellpenetrating peptides (CPPs) and cell specific MUC1 aptamer into single polyethylene
glycolated niosomes (PEGNIO) system to deliver DOX (Fig. 4.6b). The prepared
system showed a sustained delivery of DOX and excellent targeting efficiency
towards MUC1 positive Hela cells.
Aptamers can be conjugated with the lipid tail, and then the lipid tail can be
inserted into the membrane of liposome during the preparation. This is called the
preinsertion method. In addition, aptamers can also be modified onto liposomes with
the postinsertion method. Recently, Huang et al. [73] synthesized aptamer-based
dual-targeting lipid nanomicelles (NM) for enhanced delivery of gefitinib to lung
cancer-initiating cells. As shown in Fig. 4.6c, gefitinib (Gef) loaded lipid film was
synthesized by dissolving both Gef and lipid mixture in chloroform, followed by
drying the product. Next, to endow the lipid NM with active targeting ability to three
populations of cancer-initiating cells, CD133 and CD44 aptamers were modified on
the NM by reacting maleimide with sulfhydryl groups, which were from DSPE-PEG
and aptamer, respectively. This is the first time to construct drug delivery via lipid
NM for targeting multiple populations of cancer-initiating cells using aptamers. The
CD133/CD44-NM-Gef targeted both CD133
+ and CD44
+ lung cancer-initiating cells
in vivo and exhibited enhanced therapeutic efficacy against lung cancer initiating
cells than single-targeted and nontargeted nanomicelles. Thus, the as-synthesized
CD133/CD44-NM-Gef nanodrug delivery system represents a promising treatment
for lung cancer by specifically targeting lung cancer-initiating cells. Similarly, Ma
et al. [74] reported a curcumin (CUR)-loaded A15 aptamer-modified liposome for
the treatment of prostate cancer. In this system, anticancer drug CUR was encapsulated in A15 aptamer modified liposomes by the thin-film hydration technique.
This aptamer can specifically bind with CD133 molecules overexpressed on the
membrane of prostate cancer DU145 cells. In vitro experimental results showed that
blank nanoliposomes (LPs) had low cellular cytotoxicity. Both liposomes of CUR
(with or without A15 modification) exhibited a similar trend of cellular cytotoxicity
at the same concentration. When the incubation time was extended, A15-CUR LPs
showed a greater inhibitory effect on cancer cells. Cell internalization in DU145 cells
was higher for A15-CUR LPs than other treatments. The in vivo study on DU145
prostate carcinoma bearing mice showed that A15-CUR LPs reduced tumor growth
with much higher efficacy than other forms of CUR. In another study, Liu group
constructed a novel liposome where poly lactic-co-glycolic acid (PLGA) served as
the core and DSPE-PEG2000-COOH covalently linked with MUC1 S2.2 aptamer
as the shell (Fig. 4.6d) [75]. The densities of aptamer on the liposomes could be
controlled by adjusting the molar ratio of the DSPE-PEG2000-Apt conjugate to
total DSPE-PEG2000. This drug delivery system showed aptamer density-dependent
cellular uptake of nanoparticles and therapeutic effects.
To increase the flexibility of aptamer and make it better fulfill the targeting function, a short DNA strand or/and a PEG chain is usually utilized to act as a linker
between aptamer and liposome. For example, to remove the shielding effect of the
alternative binding between DNA aptamer and surrounding PEG molecules, Xing
91
in vivo, with great potential in designing similar platforms to silent other diseaserelated genes. For an enhanced cellular uptake, Seleci et al. [72] combined cellpenetrating peptides (CPPs) and cell specific MUC1 aptamer into single polyethylene
glycolated niosomes (PEGNIO) system to deliver DOX (Fig. 4.6b). The prepared
system showed a sustained delivery of DOX and excellent targeting efficiency
towards MUC1 positive Hela cells.
Aptamers can be conjugated with the lipid tail, and then the lipid tail can be
inserted into the membrane of liposome during the preparation. This is called the
preinsertion method. In addition, aptamers can also be modified onto liposomes with
the postinsertion method. Recently, Huang et al. [73] synthesized aptamer-based
dual-targeting lipid nanomicelles (NM) for enhanced delivery of gefitinib to lung
cancer-initiating cells. As shown in Fig. 4.6c, gefitinib (Gef) loaded lipid film was
synthesized by dissolving both Gef and lipid mixture in chloroform, followed by
drying the product. Next, to endow the lipid NM with active targeting ability to three
populations of cancer-initiating cells, CD133 and CD44 aptamers were modified on
the NM by reacting maleimide with sulfhydryl groups, which were from DSPE-PEG
and aptamer, respectively. This is the first time to construct drug delivery via lipid
NM for targeting multiple populations of cancer-initiating cells using aptamers. The
CD133/CD44-NM-Gef targeted both CD133
+ and CD44
+ lung cancer-initiating cells
in vivo and exhibited enhanced therapeutic efficacy against lung cancer initiating
cells than single-targeted and nontargeted nanomicelles. Thus, the as-synthesized
CD133/CD44-NM-Gef nanodrug delivery system represents a promising treatment
for lung cancer by specifically targeting lung cancer-initiating cells. Similarly, Ma
et al. [74] reported a curcumin (CUR)-loaded A15 aptamer-modified liposome for
the treatment of prostate cancer. In this system, anticancer drug CUR was encapsulated in A15 aptamer modified liposomes by the thin-film hydration technique.
This aptamer can specifically bind with CD133 molecules overexpressed on the
membrane of prostate cancer DU145 cells. In vitro experimental results showed that
blank nanoliposomes (LPs) had low cellular cytotoxicity. Both liposomes of CUR
(with or without A15 modification) exhibited a similar trend of cellular cytotoxicity
at the same concentration. When the incubation time was extended, A15-CUR LPs
showed a greater inhibitory effect on cancer cells. Cell internalization in DU145 cells
was higher for A15-CUR LPs than other treatments. The in vivo study on DU145
prostate carcinoma bearing mice showed that A15-CUR LPs reduced tumor growth
with much higher efficacy than other forms of CUR. In another study, Liu group
constructed a novel liposome where poly lactic-co-glycolic acid (PLGA) served as
the core and DSPE-PEG2000-COOH covalently linked with MUC1 S2.2 aptamer
as the shell (Fig. 4.6d) [75]. The densities of aptamer on the liposomes could be
controlled by adjusting the molar ratio of the DSPE-PEG2000-Apt conjugate to
total DSPE-PEG2000. This drug delivery system showed aptamer density-dependent
cellular uptake of nanoparticles and therapeutic effects.
To increase the flexibility of aptamer and make it better fulfill the targeting function, a short DNA strand or/and a PEG chain is usually utilized to act as a linker
between aptamer and liposome. For example, to remove the shielding effect of the
alternative binding between DNA aptamer and surrounding PEG molecules, Xing