4 Aptamer-Based Drug Delivery Systems
101
nanosponges were encoded with multivalent aptamer sequences to facilitate their
efficient delivery into cancer cells, where the acidic lysosomal microenvironment
stimulated the dissolution of ZnO into Zn
2+ ions and cleavage of DNA scaffolds,
which further induced drug release. The multivalent aptamers and intelligent drug
release showed exceptional promise and versatility for applications in biomedicine.
Another self-assembled DNA nanosponge (DNS) with densely packed antisense
oligonucleotide was also developed for the adsorption and clearance of intracellular miR-21 (Fig. 4.8e) [118]. The repeated antisense oligonucleotides efficiently
captured miR-21 and inhibited miRNAs’ function in mammalian cells.
Similar to DNA hydrogel, RNA hydrogel is another biocompatible material for
drug delivery. Ding et al. [119] developed a self-assembled RNA-triple helix hydrogel
drug delivery system for targeted therapy of triple-negative breast cancer (TNBCs)
(Fig. 4.8f). The RNA-triple helix and siRNA duplexes of CXCR4 were incorporated
into the same RNA nanoparticles. The RNA-triple helix was constructed by one tumor
suppressor miRNA (miRNA-205) and one oncogenic miRNA inhibitor (miRNA221), and both of the miRNAs showed an outstanding effect in suppression of tumors.
The siRNA duplexes of CXCR4 were embedded into the RNA hydrogel to block
breast cancer metastasis and conjugation of the LXL-DNA aptamer (apt-DNA-Chol)
provided the system with specific targeting ability to TNBCs MDA-MB-231 cells.
The in vitro and in vivo experimental results revealed that the synthesized drug
delivery system exhibited higher selectivity of absorption and controlling of miRNA
expression when compared to free miRNA and RNA transcripts. Taken all the results
together, the well-developed gene delivery system provided a potential treatment with
high specificity and selectivity toward TNBCs.
4.4.3.4 DNA or RNA Nanostructures
The modifiability of the nucleic acid structure makes aptamers easy to conjugate to
other nanoparticles. Among them, the combination of nucleic acid nanostructures
and aptamers is the typical one due to homology.
Jel et al. constructed a multifunctional DNA nanocage for fluorescence imaging
and drug delivery [120]. The DNA nanocage was fabricated by linking the cover
DNA and pedestal DNA with DNAs containing the AS1411 aptamer. The fluorescent CdTe quantum dots (QDs) were conjugated to the nanocage for the detection
of human 8-oxoG DNA glycosylase 1 (hOGG1), and DOX was inserted into DNA
duplex for cancer therapy. The DNA nanocage entered tumor cells through nucleolinmediated endocytosis, and subsequently released the DOX, providing a new platform
to combine the hOGG1 detection and chemotherapy for cancer. An tetrahedral framework nucleic acid (tFNA) was site-specifically anchored with anti-HER2 aptamer
(HApt) for selective targeting of HER2 positive breast cancer cells [121]. After
HER2-mediated endocytosis, the HApt-tFNA specifically activated the lysosomal
degradation of the membrane protein HER2. An increased HER2 digestion through
Hapt-tFNA further induced cell apoptosis and arrested cell growth.
101
nanosponges were encoded with multivalent aptamer sequences to facilitate their
efficient delivery into cancer cells, where the acidic lysosomal microenvironment
stimulated the dissolution of ZnO into Zn
2+ ions and cleavage of DNA scaffolds,
which further induced drug release. The multivalent aptamers and intelligent drug
release showed exceptional promise and versatility for applications in biomedicine.
Another self-assembled DNA nanosponge (DNS) with densely packed antisense
oligonucleotide was also developed for the adsorption and clearance of intracellular miR-21 (Fig. 4.8e) [118]. The repeated antisense oligonucleotides efficiently
captured miR-21 and inhibited miRNAs’ function in mammalian cells.
Similar to DNA hydrogel, RNA hydrogel is another biocompatible material for
drug delivery. Ding et al. [119] developed a self-assembled RNA-triple helix hydrogel
drug delivery system for targeted therapy of triple-negative breast cancer (TNBCs)
(Fig. 4.8f). The RNA-triple helix and siRNA duplexes of CXCR4 were incorporated
into the same RNA nanoparticles. The RNA-triple helix was constructed by one tumor
suppressor miRNA (miRNA-205) and one oncogenic miRNA inhibitor (miRNA221), and both of the miRNAs showed an outstanding effect in suppression of tumors.
The siRNA duplexes of CXCR4 were embedded into the RNA hydrogel to block
breast cancer metastasis and conjugation of the LXL-DNA aptamer (apt-DNA-Chol)
provided the system with specific targeting ability to TNBCs MDA-MB-231 cells.
The in vitro and in vivo experimental results revealed that the synthesized drug
delivery system exhibited higher selectivity of absorption and controlling of miRNA
expression when compared to free miRNA and RNA transcripts. Taken all the results
together, the well-developed gene delivery system provided a potential treatment with
high specificity and selectivity toward TNBCs.
4.4.3.4 DNA or RNA Nanostructures
The modifiability of the nucleic acid structure makes aptamers easy to conjugate to
other nanoparticles. Among them, the combination of nucleic acid nanostructures
and aptamers is the typical one due to homology.
Jel et al. constructed a multifunctional DNA nanocage for fluorescence imaging
and drug delivery [120]. The DNA nanocage was fabricated by linking the cover
DNA and pedestal DNA with DNAs containing the AS1411 aptamer. The fluorescent CdTe quantum dots (QDs) were conjugated to the nanocage for the detection
of human 8-oxoG DNA glycosylase 1 (hOGG1), and DOX was inserted into DNA
duplex for cancer therapy. The DNA nanocage entered tumor cells through nucleolinmediated endocytosis, and subsequently released the DOX, providing a new platform
to combine the hOGG1 detection and chemotherapy for cancer. An tetrahedral framework nucleic acid (tFNA) was site-specifically anchored with anti-HER2 aptamer
(HApt) for selective targeting of HER2 positive breast cancer cells [121]. After
HER2-mediated endocytosis, the HApt-tFNA specifically activated the lysosomal
degradation of the membrane protein HER2. An increased HER2 digestion through
Hapt-tFNA further induced cell apoptosis and arrested cell growth.