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Z. Liu and Y. Liu
Fig. 4.3 a The general construction strategies of covalent aptamer-drug conjugates. b AptamersiRNA conjugates constructed by sticky bridge modification to deliver multiplexed Anti-HIV-1
siRNAs. Reprinted with permission from Ref. [40] Copyright 2013, The American Society of Gene
& Cell Therapy. c Bispecific aptamer unit enhanced the inhibition of cell growth and induced apoptosis. Reprinted with permission from Ref. [41] Copyright 2020, Ivyspring International Publisher.
(d and e) Bivalent aptamer dual siRNA chimera targeting survivin and epidermal growth factor
receptor (EGFR) mRNA. Reprinted with permission from Ref. [42] Copyright 2016, Springer
Nature. f Bivalent aptamer-dual siRNA chimera to inhibit HIV-1 infectivity. Reprinted with permission from Ref. [43] Copyright 2015, Elsevier. g Conjugating biotinylated aptamer and siRNA to
streptavidin molecules for cancer treatment. Reprinted with permission from Ref. [44] Copyright
2013, The Royal Society of Chemistry
and siRNA to streptavidin molecules for cancer treatment (Fig. 4.3g) [44]. After
anchoring to fluorescent silver nanoclusters, this platform achieved cell type-specific
siRNA delivery and tracking.
4.3.2 Physical Intercalation
Besides covalent conjugation, physical intercalation of drugs into engineered
aptamers is another fascinating strategy for targeted drug delivery. The mechanism
is that aromatic nucleus-containing drugs, including doxorubicin (DOX), epirubicin
(EPI), and porphyrin, can physically intercalate into G-rich DNA structure or G-C
pairs of DNA double strands, due to the π–π stacking between aromatic nucleus and
DNA base pairs. In 2010, Shieh et al. reported a method to intercalate 6 molecules of
5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) into an aptamer
AS1411 with G-quadruplex structure, fabricating an apt-TMP complex (Fig. 4.4a)
[45]. The photosensitizer, TMPyP4 molecule, was found to bind tightly to the aptamer
by intercalation and outside binding. In vitro cell viability assays showed that the
Z. Liu and Y. Liu
Fig. 4.3 a The general construction strategies of covalent aptamer-drug conjugates. b AptamersiRNA conjugates constructed by sticky bridge modification to deliver multiplexed Anti-HIV-1
siRNAs. Reprinted with permission from Ref. [40] Copyright 2013, The American Society of Gene
& Cell Therapy. c Bispecific aptamer unit enhanced the inhibition of cell growth and induced apoptosis. Reprinted with permission from Ref. [41] Copyright 2020, Ivyspring International Publisher.
(d and e) Bivalent aptamer dual siRNA chimera targeting survivin and epidermal growth factor
receptor (EGFR) mRNA. Reprinted with permission from Ref. [42] Copyright 2016, Springer
Nature. f Bivalent aptamer-dual siRNA chimera to inhibit HIV-1 infectivity. Reprinted with permission from Ref. [43] Copyright 2015, Elsevier. g Conjugating biotinylated aptamer and siRNA to
streptavidin molecules for cancer treatment. Reprinted with permission from Ref. [44] Copyright
2013, The Royal Society of Chemistry
and siRNA to streptavidin molecules for cancer treatment (Fig. 4.3g) [44]. After
anchoring to fluorescent silver nanoclusters, this platform achieved cell type-specific
siRNA delivery and tracking.
4.3.2 Physical Intercalation
Besides covalent conjugation, physical intercalation of drugs into engineered
aptamers is another fascinating strategy for targeted drug delivery. The mechanism
is that aromatic nucleus-containing drugs, including doxorubicin (DOX), epirubicin
(EPI), and porphyrin, can physically intercalate into G-rich DNA structure or G-C
pairs of DNA double strands, due to the π–π stacking between aromatic nucleus and
DNA base pairs. In 2010, Shieh et al. reported a method to intercalate 6 molecules of
5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) into an aptamer
AS1411 with G-quadruplex structure, fabricating an apt-TMP complex (Fig. 4.4a)
[45]. The photosensitizer, TMPyP4 molecule, was found to bind tightly to the aptamer
by intercalation and outside binding. In vitro cell viability assays showed that the