4 Aptamer-Based Drug Delivery Systems
95
4.4.2.4 Cyclodextrin
Cyclodextrins (CDs) are naturally occurring macromolecules that are widely used as
excipients on pharmaceutical formulations. Their unique ability of acting as molecular containers by entrapping a wide range of guest molecules in internal cavity makes
them a remarkable excipient to improve drug solubility, stability, and bioavailability.
These features are especially useful when it comes to chemotherapy, because most
of the anticancer drugs have low permeability and water solubility. Therefore, guesthost inclusion complexes offer several potential advantages not only regarding the
improvement of pharmaceutical formulations’ characteristics but also considering
the reduction of drugs’ toxic side effects [90].
Aptamers can be conjugated with CDs to construct targeted drug delivery systems.
For example, Jia et al. [91] recently reported an AS1411@PEGMA@GQD@γCD-MOF nanocomposite for anticancer drug delivery (Fig. 4.7b). Here, AS1411
aptamer acted as a targeting agent which specifically bind to nucleolin overexpressed cancer cells. Poly(ethyleneglycol) dimethacrylate (PEGMA) was utilized
as the pH responsive material. Graphene quantum dots (GQDs) were embedded in
the γ-CD-MOF matrix and endowed the system with strong fluorescence. Large
amounts of anticancer drug DOX were encapsulated within this composite attributed
to the chemical-rich functionality. The targeting specificity experiments revealed that
these drug carriers were effectively internalized through receptor-mediated endocytosis pathway. The in vivo antitumor study on tumor-bearing mice model demonstrated effective suppression of tumor growth with negligible side effects after treatments. Therefore, the prepared AS1411@PEGMA@GQD@γ-CD-MOF nanocomposite has great potential in anticancer therapy to deliver desired drugs and inhibit
tumor growth both in vitro and in vivo. Interestingly, Jang et al. [92] prepared a
polyrotaxane-based platform for delivering chemotherapeutic drug to lymphoblastic
leukemia cells (Fig. 4.7c). In this system, the CDs were covalently conjugated with
lymphoblast targeting aptamers and pH-responsive “i-motif” DNA complements,
which induced CDs’ assembly via i-motif dsDNA annealing. PEG served as a tread
along which target aptamer was slide for selective binding towards target cells.
The G-C rich i-motif dsDNA enabled the incorporation of DOX, where intracellular acidic environment dissociated the dsDNA to release chemotherapeutic DOX.
These combined features caused effective inhibition of lymphoblastic leukemias both
in vitro and in vivo. In another study, Li et al. [93] applied pluronic F127/cyclodextrinlinked polymer composite micelles as the carrier, and AS1411 aptamer as the
targeting agent, to load and deliver DOX for the therapy of breast cancer. The pharmacokinetic study demonstrated that the prepared DOX-CM-Ap drug delivery system
could significantly prolong the blood circulation time of DOX than free DOX. Moreover, in vivo real-time imaging study showed that aptamer-modified micelles had
better tumor targeting ability than nontargeted micelles. Taking the advantages of the
nucleolin-mediated endocytosis pathway and controllable cellular release of DOX,
DOX-CM-Ap was validated to enhance the anti-tumor efficacy of DOX in vivo.
95
4.4.2.4 Cyclodextrin
Cyclodextrins (CDs) are naturally occurring macromolecules that are widely used as
excipients on pharmaceutical formulations. Their unique ability of acting as molecular containers by entrapping a wide range of guest molecules in internal cavity makes
them a remarkable excipient to improve drug solubility, stability, and bioavailability.
These features are especially useful when it comes to chemotherapy, because most
of the anticancer drugs have low permeability and water solubility. Therefore, guesthost inclusion complexes offer several potential advantages not only regarding the
improvement of pharmaceutical formulations’ characteristics but also considering
the reduction of drugs’ toxic side effects [90].
Aptamers can be conjugated with CDs to construct targeted drug delivery systems.
For example, Jia et al. [91] recently reported an AS1411@PEGMA@GQD@γCD-MOF nanocomposite for anticancer drug delivery (Fig. 4.7b). Here, AS1411
aptamer acted as a targeting agent which specifically bind to nucleolin overexpressed cancer cells. Poly(ethyleneglycol) dimethacrylate (PEGMA) was utilized
as the pH responsive material. Graphene quantum dots (GQDs) were embedded in
the γ-CD-MOF matrix and endowed the system with strong fluorescence. Large
amounts of anticancer drug DOX were encapsulated within this composite attributed
to the chemical-rich functionality. The targeting specificity experiments revealed that
these drug carriers were effectively internalized through receptor-mediated endocytosis pathway. The in vivo antitumor study on tumor-bearing mice model demonstrated effective suppression of tumor growth with negligible side effects after treatments. Therefore, the prepared AS1411@PEGMA@GQD@γ-CD-MOF nanocomposite has great potential in anticancer therapy to deliver desired drugs and inhibit
tumor growth both in vitro and in vivo. Interestingly, Jang et al. [92] prepared a
polyrotaxane-based platform for delivering chemotherapeutic drug to lymphoblastic
leukemia cells (Fig. 4.7c). In this system, the CDs were covalently conjugated with
lymphoblast targeting aptamers and pH-responsive “i-motif” DNA complements,
which induced CDs’ assembly via i-motif dsDNA annealing. PEG served as a tread
along which target aptamer was slide for selective binding towards target cells.
The G-C rich i-motif dsDNA enabled the incorporation of DOX, where intracellular acidic environment dissociated the dsDNA to release chemotherapeutic DOX.
These combined features caused effective inhibition of lymphoblastic leukemias both
in vitro and in vivo. In another study, Li et al. [93] applied pluronic F127/cyclodextrinlinked polymer composite micelles as the carrier, and AS1411 aptamer as the
targeting agent, to load and deliver DOX for the therapy of breast cancer. The pharmacokinetic study demonstrated that the prepared DOX-CM-Ap drug delivery system
could significantly prolong the blood circulation time of DOX than free DOX. Moreover, in vivo real-time imaging study showed that aptamer-modified micelles had
better tumor targeting ability than nontargeted micelles. Taking the advantages of the
nucleolin-mediated endocytosis pathway and controllable cellular release of DOX,
DOX-CM-Ap was validated to enhance the anti-tumor efficacy of DOX in vivo.