98
Z. Liu and Y. Liu
coated by BSA exhibited no significant toxicity. The AS1411 aptamer modification also dramatically improved the affinity of the drug-loaded nanoplatform toward
breast cancer cells, suggesting the potential of the synthesized DOX@apt-BSA
IONPs-GNPs in photothermal therapy and MRI imaging.
4.4.3.2 Protamine
Protamine is a natural cationic peptide whose sulfate salt forms have been applied
in clinical application [103]. In a study, protamine has also been used to prolong
the thrombin-inhibiting effect of DNA aptamer in vivo [104]. Zeng et al. [105]
applied protamine as the nanocarrier and aptamer as the targeting agent to construct a
drug-loaded nanoparticle for precise lymphoma therapy. CD30 specific aptamer was
modified on protamine and DOX was loaded between the dsDNA for chemotherapy.
siRNA for oncogene silencing was adsorbed on the surface of the nanomaterial
by noncovalent charge-force reaction. It is demonstrated that the protamine-based
nanoparticles specifically binded to lymphoma cells with the guidance of CD30
aptamer, but did not respond to nontarget cells in control experiments. By combining
cell-selective chemotherapy and gene therapy, the synthesized nanoparticles showed
little toxicity to none-target cells but exhibited effective cytotoxicity to lymphoma
cells. In another study, protamine was employed to deliver CRISPR-Cas9 plasmid (a
genome editing plasmid) to target cancer cells, which can reverse tumor malignization through genome editing (Fig. 4.7e) [95]. MUC1 aptamer for targeting MUC1
protein overexpressed cancer cells and AS1411 aptamer for targeting nucleolin overexpressed cells were modified with heparin on protamine@CRISPR-Cas9 plasmid
nanoparticles. The down-regulation of a series of tumor growth factors indicated that
the genome editing system effectively suppressed cancerous cell growth. Later, Liu
et al. [106] decorated protamine@Cas9/sgRNA plasmids nanoparticles with AS1411
aptamer and nuclear location sequence (NLS) peptide. Under the dual targeting effect
of NLS peptide and AS1411, Cas9/sgRNA plasmids were effectively delivered to
the nucleus of tumor cells, knocking out the protein tyrosine kinase 2 (PTK2) gene
and thus down-regulating focal adhesion kinase (FAK).
4.4.3.3 DNA or RNA Hydrogel
Hydrogels are 3D networks of cross-linked hydrophilic polymer chains [107].
Aptamers can be embedded into hydrogels to construct drug delivery systems for
targeted cancer therapy. Due to its homology and chemical modifiability, DNA
hydrogel are excellent carriers for the delivery of both gene therapeutic molecules
and chemical anticancer agents [108, 109]. In an illustrative example of gene therapeutic molecules, a DNA prism with adjustable number of Rab26 siRNA and MUC-1
aptamer successfully inhibited target gene expression and cancer cell proliferation
Z. Liu and Y. Liu
coated by BSA exhibited no significant toxicity. The AS1411 aptamer modification also dramatically improved the affinity of the drug-loaded nanoplatform toward
breast cancer cells, suggesting the potential of the synthesized DOX@apt-BSA
IONPs-GNPs in photothermal therapy and MRI imaging.
4.4.3.2 Protamine
Protamine is a natural cationic peptide whose sulfate salt forms have been applied
in clinical application [103]. In a study, protamine has also been used to prolong
the thrombin-inhibiting effect of DNA aptamer in vivo [104]. Zeng et al. [105]
applied protamine as the nanocarrier and aptamer as the targeting agent to construct a
drug-loaded nanoparticle for precise lymphoma therapy. CD30 specific aptamer was
modified on protamine and DOX was loaded between the dsDNA for chemotherapy.
siRNA for oncogene silencing was adsorbed on the surface of the nanomaterial
by noncovalent charge-force reaction. It is demonstrated that the protamine-based
nanoparticles specifically binded to lymphoma cells with the guidance of CD30
aptamer, but did not respond to nontarget cells in control experiments. By combining
cell-selective chemotherapy and gene therapy, the synthesized nanoparticles showed
little toxicity to none-target cells but exhibited effective cytotoxicity to lymphoma
cells. In another study, protamine was employed to deliver CRISPR-Cas9 plasmid (a
genome editing plasmid) to target cancer cells, which can reverse tumor malignization through genome editing (Fig. 4.7e) [95]. MUC1 aptamer for targeting MUC1
protein overexpressed cancer cells and AS1411 aptamer for targeting nucleolin overexpressed cells were modified with heparin on protamine@CRISPR-Cas9 plasmid
nanoparticles. The down-regulation of a series of tumor growth factors indicated that
the genome editing system effectively suppressed cancerous cell growth. Later, Liu
et al. [106] decorated protamine@Cas9/sgRNA plasmids nanoparticles with AS1411
aptamer and nuclear location sequence (NLS) peptide. Under the dual targeting effect
of NLS peptide and AS1411, Cas9/sgRNA plasmids were effectively delivered to
the nucleus of tumor cells, knocking out the protein tyrosine kinase 2 (PTK2) gene
and thus down-regulating focal adhesion kinase (FAK).
4.4.3.3 DNA or RNA Hydrogel
Hydrogels are 3D networks of cross-linked hydrophilic polymer chains [107].
Aptamers can be embedded into hydrogels to construct drug delivery systems for
targeted cancer therapy. Due to its homology and chemical modifiability, DNA
hydrogel are excellent carriers for the delivery of both gene therapeutic molecules
and chemical anticancer agents [108, 109]. In an illustrative example of gene therapeutic molecules, a DNA prism with adjustable number of Rab26 siRNA and MUC-1
aptamer successfully inhibited target gene expression and cancer cell proliferation