96
Z. Liu and Y. Liu
4.4.2.5 Other Organic Materials
In this section, we briefly introduced some other organic materials, to which aptamers
can be conjugated for constructing targeted drug delivery systems.
Polydopamine (PDA) is a mussel-inspired polymer derived from the polymerization of dopamine in an alkaline environment [96]. It has good biocompatibility
and photothermal property. PDA can deposit on most of solid surfaces whether
hydrophilic or hydrophobic. Because of the abundant quinone structure, PDA can link
with nucleophilic groups (e.g., thiolor amine) containing ligands via Michael addition reaction and/or Schiff base reaction. So, PDA is a commonly used modification
material in drug delivery systems [97]. Tao et al. [98] reported a simple polydopamine
(pD)-based surface modification method to prepare novel nanoparticle-aptamer
bioconjugates (Apt-pD-DTX/NPs) for in vivo treatment of breast cancer. Docetaxel
(DTX) loaded star-shaped copolymer CA-PLGA-b-D-α-tocopheryl polyethylene
glycol 1000 succinate (TPGS) nanoparticles were prepared firstly. Then, pD was
coated on the nanoparticles in alkaline condition. Finally, thiol-terminated AS1411
aptamer was modified on the nanoparticles by Michael addition reaction. Both
in vitro cell experiments and in vivo animal studies demonstrated that the prepared
Apt-pD-DTX nanoparticles achieved high targeting efficiency and enhanced therapeutic effects compared with clinical Taxotere
® and nanoparticles without aptamer
modification.
Chimeric polymersomes with matrix metalloproteinase 2 (MMP-2) responsiveness were reported to treat colorectal cancer [99]. In this nanostructure, polyethylene glycol (PEG) was linked to polylactide (PLA) through the synthetic peptide
PVGLIG. The peptide can be selectively cleaved by the tumor-associated MMP-2
enzyme. The hydrophobic drug SN38 was loaded into the synthesized polymersomes with high encapsulation efficiency. To endow the polymersomes with active
targeting ability to cancer cells, AS1411 aptamer was modified onto the surface of
MMP-2 responsive polymersomes, endowing the system with specific binding to the
nucleolin overexpressed cancer cells. The prepared chimeric polymersomes formulation showed controlled release of SN38 at physiological condition. However, in
the presence of MMP-2 enzyme, the release rate increased to seven folds. In vitro
cellular toxicity experiments against nucleolin positive C26 cell line demonstrated
that the targeted polymersomes had much higher toxicity to the cancer cells than
nontargeted ones. In addition, the synthesized MMP-2 responsive chimeric polymersomes exhibited higher therapeutic index than other treatment groups in vivo. All
the results strongly confirmed that the as-synthesized MMP-2 responsive chimeric
polymersomes provided favorable characteristics as an ideal delivery system against
colorectal cancer.
In another study, Khezrian et al. [100] synthesized functional amphiphilic Janus
nanoparticles (JNP), which consisted of hydrophilic and hydrophobic biocompatible polymers as two distinct sides, for targeted therapy of human colorectal adenocarcinoma. The authors functionalized the surface-active hydrophilic side of this
Janus platform with an aptamer, which can specifically bind to epithelial cell adhesion molecule (EpCAM) to deliver DOX for the treatment of metastasis colorectal
Z. Liu and Y. Liu
4.4.2.5 Other Organic Materials
In this section, we briefly introduced some other organic materials, to which aptamers
can be conjugated for constructing targeted drug delivery systems.
Polydopamine (PDA) is a mussel-inspired polymer derived from the polymerization of dopamine in an alkaline environment [96]. It has good biocompatibility
and photothermal property. PDA can deposit on most of solid surfaces whether
hydrophilic or hydrophobic. Because of the abundant quinone structure, PDA can link
with nucleophilic groups (e.g., thiolor amine) containing ligands via Michael addition reaction and/or Schiff base reaction. So, PDA is a commonly used modification
material in drug delivery systems [97]. Tao et al. [98] reported a simple polydopamine
(pD)-based surface modification method to prepare novel nanoparticle-aptamer
bioconjugates (Apt-pD-DTX/NPs) for in vivo treatment of breast cancer. Docetaxel
(DTX) loaded star-shaped copolymer CA-PLGA-b-D-α-tocopheryl polyethylene
glycol 1000 succinate (TPGS) nanoparticles were prepared firstly. Then, pD was
coated on the nanoparticles in alkaline condition. Finally, thiol-terminated AS1411
aptamer was modified on the nanoparticles by Michael addition reaction. Both
in vitro cell experiments and in vivo animal studies demonstrated that the prepared
Apt-pD-DTX nanoparticles achieved high targeting efficiency and enhanced therapeutic effects compared with clinical Taxotere
® and nanoparticles without aptamer
modification.
Chimeric polymersomes with matrix metalloproteinase 2 (MMP-2) responsiveness were reported to treat colorectal cancer [99]. In this nanostructure, polyethylene glycol (PEG) was linked to polylactide (PLA) through the synthetic peptide
PVGLIG. The peptide can be selectively cleaved by the tumor-associated MMP-2
enzyme. The hydrophobic drug SN38 was loaded into the synthesized polymersomes with high encapsulation efficiency. To endow the polymersomes with active
targeting ability to cancer cells, AS1411 aptamer was modified onto the surface of
MMP-2 responsive polymersomes, endowing the system with specific binding to the
nucleolin overexpressed cancer cells. The prepared chimeric polymersomes formulation showed controlled release of SN38 at physiological condition. However, in
the presence of MMP-2 enzyme, the release rate increased to seven folds. In vitro
cellular toxicity experiments against nucleolin positive C26 cell line demonstrated
that the targeted polymersomes had much higher toxicity to the cancer cells than
nontargeted ones. In addition, the synthesized MMP-2 responsive chimeric polymersomes exhibited higher therapeutic index than other treatment groups in vivo. All
the results strongly confirmed that the as-synthesized MMP-2 responsive chimeric
polymersomes provided favorable characteristics as an ideal delivery system against
colorectal cancer.
In another study, Khezrian et al. [100] synthesized functional amphiphilic Janus
nanoparticles (JNP), which consisted of hydrophilic and hydrophobic biocompatible polymers as two distinct sides, for targeted therapy of human colorectal adenocarcinoma. The authors functionalized the surface-active hydrophilic side of this
Janus platform with an aptamer, which can specifically bind to epithelial cell adhesion molecule (EpCAM) to deliver DOX for the treatment of metastasis colorectal