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Z. Liu and Y. Liu
aptamer served as the trigger to induce hybridization chain reaction (HCR) on the
cell surface for activatable tumor imaging and accumulation of high-load prodrugs
(Fig. 4.9d) [127]. The platform provided high-contrast fluorescence imaging of tumor
cells, which rendered high-efficient cellular uptake of drugs. Not only a single one but
also multiple aptamers could work together. Zou et al. [128] designed pH-stimulated
multivalent DNA assemblies (MDAs) with controllable targeting ability at physiological temperature (Fig. 4.9e). The aptamer-based DNA monomer (AptDM) was
composed by Cy5 labeled aptamer strands and a Y-shaped DNA scaffold containing
split i-motif tails. Two split i-motif could fold into quadruplex structure in acidic
environment. The anticancer drug DOX was loaded into GC base pairs of AptDM.
At neutral environment, AptDMs were existed as well dispersed small units. While
in acidic environment, AptDMs crosslinked into multivalent systems with specifically improved affinity. The experimental results demonstrated that MDAs with low
cytotoxicity to normal cells have higher affinity to cancer cells at 37°C, thereby
allowing high-sensitive diagnosis, efficient drug delivery, and improved suppression
to tumor cells. A novel multiple aptamer-mediated method was applied in DNA
nanoscale precision-guided missile (D-PGM) to achieve precise delivery of drugs
(Fig. 4.9f) [129]. The D-PGM consisted of a warhead (WH) and a guidance (GC).
The WH was a rod-like DNA carrier for loading DOX. The GC was a DNA logic
circuit assembled by four DNA strands including P0, P1, P2, and P3, where P1, P2,
and P3 were partly complementary to TC01, Sgc4f, and Sgc8 aptamers, respectively.
Three adapted aptamers were injected into tumor-bearing mice first. It was found that
aptamers located on the surface of targeted cells via ligand-receptor interaction, and
the locked GC of D-PGM was unlocked by Sgc8, Sgc4f, and TC01 gradually. Finally,
D-PGM was internalized by cancer cells via TC01 receptor-mediated endocytosis.
The GC logic gates precisely guided DOX-loaded WH toward target cancer cells,
thereby leading to highly selective and enhanced therapeutic efficacy. Nucleolin can
also serve as molecular trigger for mechanical opening of the DNA nanorobot, thus
entrapping and releasing the thrombin specifically to tumor-associated blood vessels
for tumor necrosis [130]. The system depended on introducing AS1411 aptamer
sequences and their complements into rectangular origami sheet, which enabled the
rolling of the nanosheets into nanotubes via DNA hybridization. The nucleolin could
competitively bind with AS1411 aptamer to dissociate the dsDNA, causing the open
of the nanotube to release the entrapped agents. This novel DNA robot shows great
potential in precise drug delivery in cancer therapy. Besides, Li et al. introduced ATP
aptamer and i-motif structure into a DNA framework for logic imaging of lysosomal
pH and ATP (Fig. 4.9g) [131]. Considering the abnormal levels of pH and ATP in
various diseased cells, the designed logic device might be extended to control drug
release for disease treatment.
Z. Liu and Y. Liu
aptamer served as the trigger to induce hybridization chain reaction (HCR) on the
cell surface for activatable tumor imaging and accumulation of high-load prodrugs
(Fig. 4.9d) [127]. The platform provided high-contrast fluorescence imaging of tumor
cells, which rendered high-efficient cellular uptake of drugs. Not only a single one but
also multiple aptamers could work together. Zou et al. [128] designed pH-stimulated
multivalent DNA assemblies (MDAs) with controllable targeting ability at physiological temperature (Fig. 4.9e). The aptamer-based DNA monomer (AptDM) was
composed by Cy5 labeled aptamer strands and a Y-shaped DNA scaffold containing
split i-motif tails. Two split i-motif could fold into quadruplex structure in acidic
environment. The anticancer drug DOX was loaded into GC base pairs of AptDM.
At neutral environment, AptDMs were existed as well dispersed small units. While
in acidic environment, AptDMs crosslinked into multivalent systems with specifically improved affinity. The experimental results demonstrated that MDAs with low
cytotoxicity to normal cells have higher affinity to cancer cells at 37°C, thereby
allowing high-sensitive diagnosis, efficient drug delivery, and improved suppression
to tumor cells. A novel multiple aptamer-mediated method was applied in DNA
nanoscale precision-guided missile (D-PGM) to achieve precise delivery of drugs
(Fig. 4.9f) [129]. The D-PGM consisted of a warhead (WH) and a guidance (GC).
The WH was a rod-like DNA carrier for loading DOX. The GC was a DNA logic
circuit assembled by four DNA strands including P0, P1, P2, and P3, where P1, P2,
and P3 were partly complementary to TC01, Sgc4f, and Sgc8 aptamers, respectively.
Three adapted aptamers were injected into tumor-bearing mice first. It was found that
aptamers located on the surface of targeted cells via ligand-receptor interaction, and
the locked GC of D-PGM was unlocked by Sgc8, Sgc4f, and TC01 gradually. Finally,
D-PGM was internalized by cancer cells via TC01 receptor-mediated endocytosis.
The GC logic gates precisely guided DOX-loaded WH toward target cancer cells,
thereby leading to highly selective and enhanced therapeutic efficacy. Nucleolin can
also serve as molecular trigger for mechanical opening of the DNA nanorobot, thus
entrapping and releasing the thrombin specifically to tumor-associated blood vessels
for tumor necrosis [130]. The system depended on introducing AS1411 aptamer
sequences and their complements into rectangular origami sheet, which enabled the
rolling of the nanosheets into nanotubes via DNA hybridization. The nucleolin could
competitively bind with AS1411 aptamer to dissociate the dsDNA, causing the open
of the nanotube to release the entrapped agents. This novel DNA robot shows great
potential in precise drug delivery in cancer therapy. Besides, Li et al. introduced ATP
aptamer and i-motif structure into a DNA framework for logic imaging of lysosomal
pH and ATP (Fig. 4.9g) [131]. Considering the abnormal levels of pH and ATP in
various diseased cells, the designed logic device might be extended to control drug
release for disease treatment.