4 Aptamer-Based Drug Delivery Systems
103
sequence was tailed with AS1411 aptamer, which specifically bound with the nucleolin overexpressed on CT26 cancer cells to promote the drug delivery efficiency.
Confocal microscopy experiments revealed that the prepared drug delivery system
selectively delivered DOX into CT26 colon cancer cells but not into the control cells.
Compared with free DOX, Apt-HJ-DOX significantly enhanced the antitumor efficacy in vivo with negligible adverse effects. All the results suggested that AS1411
aptamer-modified DNA nanocross has the potential for targeted therapy of colon
cancer.
Compared with DNA nanostructures, RNA nanostructures are mainly used for
gene therapeutic molecule delivery. For example, Yin et al. [124] reported an RNA
nanoparticle-based drug delivery system for the gene therapy of triple-negative breast
cancer (TNBC). This system was constructed mainly by three parts: RNA sequence
as the carrier, one locked nuclei acid (LNA) sequence for miRNA21 inhibition, and
CD133 RNA aptamer as the targeting agent. The binding assays demonstrated the
specific uptake of the RNA nanoparticles to breast cancer stem cells (BCSCs) and
TNBC cells. Also, the cancer cell migration was significantly reduced, and miR21
expression level was inhibited.
4.4.4 Others
Besides using aptamers for accurate cell targeting, developing drug delivery systems
also depends on intelligent moieties for controlled drug release. In PDT, NIRexcitable upconversion nanoparticle (UCNP) is a popular material to provide NIR
light into deeper tissues for treatment. Lin et al. [125] fabricated an aptamer-guided
UCNP for targeted drug delivery and NIR light-triggered PDT. Protoporphyrin
IX (PpIX), a photosensitizer, was loaded in the Apt-UCNP nanosphere. The assynthesized nanospheres exhibited efficient cellular uptake to cancerous cells, which
was attributed to the specific interaction of AS1411 and overexpressed nucleolin.
Under the irradiation of NIR, it is observed that the cellular ROS level was obviously
enhanced after incubation with PpIX-Apt-UCNP nanospheres, and the cells were
also induced to apoptosis. In another study, Tan et al. [126] constructed aptamerfunctionalized calcium carbonate (CaCO 3 ) with pH responsiveness for targeted
delivery of DOX. The CaCO 3 nanoparticles were dissolved at relatively low lysosome
pH (4.5-5.5), thus facilitated the release of DOX.
Moreover, the development of DNA nanotechnology enables the construction
of various DNA nanostructures with different 2D/3D architectures to deliver anticancer agents (Fig. 4.9c). The dynamic DNA assembly has recently been emerged
as a novel platform, which could responsive to environment stimuli with specific
behaviors, the underling mechanisms have been systematically summarized by Liu
group [111]. Introducing intelligent moieties endows these DNA nanostructures with
responsiveness to various stimuli for controlled drug release. A structure-switching
103
sequence was tailed with AS1411 aptamer, which specifically bound with the nucleolin overexpressed on CT26 cancer cells to promote the drug delivery efficiency.
Confocal microscopy experiments revealed that the prepared drug delivery system
selectively delivered DOX into CT26 colon cancer cells but not into the control cells.
Compared with free DOX, Apt-HJ-DOX significantly enhanced the antitumor efficacy in vivo with negligible adverse effects. All the results suggested that AS1411
aptamer-modified DNA nanocross has the potential for targeted therapy of colon
cancer.
Compared with DNA nanostructures, RNA nanostructures are mainly used for
gene therapeutic molecule delivery. For example, Yin et al. [124] reported an RNA
nanoparticle-based drug delivery system for the gene therapy of triple-negative breast
cancer (TNBC). This system was constructed mainly by three parts: RNA sequence
as the carrier, one locked nuclei acid (LNA) sequence for miRNA21 inhibition, and
CD133 RNA aptamer as the targeting agent. The binding assays demonstrated the
specific uptake of the RNA nanoparticles to breast cancer stem cells (BCSCs) and
TNBC cells. Also, the cancer cell migration was significantly reduced, and miR21
expression level was inhibited.
4.4.4 Others
Besides using aptamers for accurate cell targeting, developing drug delivery systems
also depends on intelligent moieties for controlled drug release. In PDT, NIRexcitable upconversion nanoparticle (UCNP) is a popular material to provide NIR
light into deeper tissues for treatment. Lin et al. [125] fabricated an aptamer-guided
UCNP for targeted drug delivery and NIR light-triggered PDT. Protoporphyrin
IX (PpIX), a photosensitizer, was loaded in the Apt-UCNP nanosphere. The assynthesized nanospheres exhibited efficient cellular uptake to cancerous cells, which
was attributed to the specific interaction of AS1411 and overexpressed nucleolin.
Under the irradiation of NIR, it is observed that the cellular ROS level was obviously
enhanced after incubation with PpIX-Apt-UCNP nanospheres, and the cells were
also induced to apoptosis. In another study, Tan et al. [126] constructed aptamerfunctionalized calcium carbonate (CaCO 3 ) with pH responsiveness for targeted
delivery of DOX. The CaCO 3 nanoparticles were dissolved at relatively low lysosome
pH (4.5-5.5), thus facilitated the release of DOX.
Moreover, the development of DNA nanotechnology enables the construction
of various DNA nanostructures with different 2D/3D architectures to deliver anticancer agents (Fig. 4.9c). The dynamic DNA assembly has recently been emerged
as a novel platform, which could responsive to environment stimuli with specific
behaviors, the underling mechanisms have been systematically summarized by Liu
group [111]. Introducing intelligent moieties endows these DNA nanostructures with
responsiveness to various stimuli for controlled drug release. A structure-switching