92
Z. Liu and Y. Liu
et al. [76] chose oligo-thymine as a spacer with appropriate length and inserted it
between aptamer and PEG-modified liposome. They found that the spacer length is
a critical factor in determining the targeting ability of the system, regardless of the
composition of the spacer. Li et al. [77] reported a liposome-based drug delivery
system, which delivered anti-BRAF siRNA (siBraf) to treat melanomas. They first
prepared siBraf-loaded PEGylated cationic liposome and then modified AS1411
aptamer on it by bifunctional PEG linker for targeting nucleolin. The complex showed
specific binding to nucleolin positive cancer cells and strong silencing activity toward
BRAF gene.
4.4.2.2 Extracellular Vesicles (EVs)
Extracellular vesicles (EVs) derived from live cells can maintain the cell membrane
natures, thus holding great potential as liposome alternatives in biological applications. EVs contain two main categories: micro-vesicles and exosomes [79].
Tan et al. [78] recently applied Hela cell-derived giant membrane vesicles
to deliver multiple therapeutic drugs for targeted cancer therapy (Fig. 4.6e).
Various therapeutic drugs, including AS1411 aptamer, photosensitizer TMPyP4
and photothermal therapy (PTT) agentindocyanine green (ICG), were efficiently
encapsulated into giant membrane vesicles. Based on membrane fusion, the vesicles
were uptaken by target cells, causing synergistic photodynamic/photothermal therapy
under light irradiation. Using cholesterol to mediate aptamer AS1411 insertion, Wang
et al. [80] employed EVs as vectors to deliver let-7 miRNA or VEGF siRNA to
target cancer cells. This drug-loaded EVs selectively inhibited tumor growth without
obvious immunogenicity or noticeable toxicity. In another EVs-based nanoplatform
for the delivery of survivin siRNA, Pi et al. [81] decorated EVs with arrow-shaped
RNA ligands, which was constructed by incorporating RNA aptamer into a three-way
junction (3WJ). They incorporated PSMA RNA aptamer and EGFR RNA aptamer
into 3WJ to form PSMA-3WJ and EGFR-3WJ, respectively. Compared with the
control group, the efficacy of cancer inhibition of RND ligand-modified EVS/survivin
siRNA was significantly enhanced.
Moreover, exosomes are other intriguing EVs for drug delivery. Luo et al. [82]
decorated bone marrow stromal cell (ST)-derived exosomes (STExos) with bone
marrow mesenchymal stem cells (BMSC)-specific aptamers to promote bone regeneration. The aptamer increased the in vitro internalization of STExo into BMSCs and
the in vivo accumulation of STExo in bone, which avoided rapid metabolism and
clearance, thereby promoting bone regeneration. Zou et al. [83] fabricated aptamerfunctionalized exosomes (Apt-Exos) for specific delivery of molecular therapeutics.
Aptamer Sgc8 was modified on the surface of DOX-loaded Exos via diacyllipid-PEG
linker. The therapeutic efficacy of DOX-loaded Sgc8-Exos was stronger than that of
free DOX due to the enhanced cellular accumulation.
Z. Liu and Y. Liu
et al. [76] chose oligo-thymine as a spacer with appropriate length and inserted it
between aptamer and PEG-modified liposome. They found that the spacer length is
a critical factor in determining the targeting ability of the system, regardless of the
composition of the spacer. Li et al. [77] reported a liposome-based drug delivery
system, which delivered anti-BRAF siRNA (siBraf) to treat melanomas. They first
prepared siBraf-loaded PEGylated cationic liposome and then modified AS1411
aptamer on it by bifunctional PEG linker for targeting nucleolin. The complex showed
specific binding to nucleolin positive cancer cells and strong silencing activity toward
BRAF gene.
4.4.2.2 Extracellular Vesicles (EVs)
Extracellular vesicles (EVs) derived from live cells can maintain the cell membrane
natures, thus holding great potential as liposome alternatives in biological applications. EVs contain two main categories: micro-vesicles and exosomes [79].
Tan et al. [78] recently applied Hela cell-derived giant membrane vesicles
to deliver multiple therapeutic drugs for targeted cancer therapy (Fig. 4.6e).
Various therapeutic drugs, including AS1411 aptamer, photosensitizer TMPyP4
and photothermal therapy (PTT) agentindocyanine green (ICG), were efficiently
encapsulated into giant membrane vesicles. Based on membrane fusion, the vesicles
were uptaken by target cells, causing synergistic photodynamic/photothermal therapy
under light irradiation. Using cholesterol to mediate aptamer AS1411 insertion, Wang
et al. [80] employed EVs as vectors to deliver let-7 miRNA or VEGF siRNA to
target cancer cells. This drug-loaded EVs selectively inhibited tumor growth without
obvious immunogenicity or noticeable toxicity. In another EVs-based nanoplatform
for the delivery of survivin siRNA, Pi et al. [81] decorated EVs with arrow-shaped
RNA ligands, which was constructed by incorporating RNA aptamer into a three-way
junction (3WJ). They incorporated PSMA RNA aptamer and EGFR RNA aptamer
into 3WJ to form PSMA-3WJ and EGFR-3WJ, respectively. Compared with the
control group, the efficacy of cancer inhibition of RND ligand-modified EVS/survivin
siRNA was significantly enhanced.
Moreover, exosomes are other intriguing EVs for drug delivery. Luo et al. [82]
decorated bone marrow stromal cell (ST)-derived exosomes (STExos) with bone
marrow mesenchymal stem cells (BMSC)-specific aptamers to promote bone regeneration. The aptamer increased the in vitro internalization of STExo into BMSCs and
the in vivo accumulation of STExo in bone, which avoided rapid metabolism and
clearance, thereby promoting bone regeneration. Zou et al. [83] fabricated aptamerfunctionalized exosomes (Apt-Exos) for specific delivery of molecular therapeutics.
Aptamer Sgc8 was modified on the surface of DOX-loaded Exos via diacyllipid-PEG
linker. The therapeutic efficacy of DOX-loaded Sgc8-Exos was stronger than that of
free DOX due to the enhanced cellular accumulation.