12.3.2 Macromolecules
Also, there are huge varieties of macromolecules which can target the specific
disease or diseased site. Any kinds of macromolecules with 3D structures that can
interact with target proteins, including antibody or its fragments, protein, affibody
® ,
nucleic acid, nucleic acid aptamer, and peptide aptamer, can be used or developed
as a targeting ligand molecule for nanomedicine.
First famous targeting molecules are the antibodies and their fragments. The
antibody has two epitope binding sites in a single molecule and offers an exceedingly high selectivity and binding affinity for the target proteins of interest. Several
antibodies are used in clinic by approval of FDA. Hadjipanayis et al. [37] employed
an antibody against epidermal growth factor receptor (EGFR) deletion mutant to
fabricate iron oxide nanoparticles for targeted imaging and therapeutic treatment of
glioblastoma. Selective binding to this mutant EGFR was achieved by creating a
polyclonal rabbit antibody toward the chemically synthesized 14-amino-acid fusion
junction sequence (EGFRvIIIAb). Covalent conjugation of the purified rabbit
polyclonal EGFRvIIIAb to the amphiphilic triblock copolymer-coated iron oxide
nanoparticles showed glioblastoma-targeting ability as a potential theranostic agent.
Even though the well-established targeting ability and selectivity of antibody itself,
antibody fragment is used frequently as a targeting molecules for nanomaterials,
because of the relatively large size of antibody with 10–15 nm (150 kDa) compared
to nanomaterials. Ling et al. reported iron oxide nanoparticles with the single chain
anti-prostate stem cell antigen (PSCA) antibody fragment (scAbP-SCA) as a
specific targeting molecule for prostate cancer targeted imaging and therapy [38]. In
a similar way, Chen et al. constructed iron oxide and non-viral polymeric vector
nanocomposite using a CD3 single chain antibody (scAbCD3) as a targeting
molecules for gene delivery to T cells [39]. Antibody-conjugated liposomes, so
called immunoliposomes, are common pharmaceutical carriers for targeted drug
delivery because of their unique ability to encapsulate both hydrophilic and
hydrophobic therapeutic agents. Lu et al. developed in vivo lung cancer targeting
immunoliposomes using an anti-c-Met single chain variable fragment (scFv) antibody [40].
Aptamers are small nucleic acid ligands (15–40 bases) and used as targeting
molecules that bind to targets with high specificity due to the ability of the molecules to fold into unique conformations with three-dimensional structures [41].
Aptamers have potential advantage over antibodies, such as the small size
(15 kDa), low immunogenicity, and easy scale-up preparation without
batch-to-batch variations. Lupold et al. identified 2′-fluoro-pyridine-RNA aptamers
generated against the extracellular domain of prostate-specific membrane antigen
(PSMA) [42] and attached on self-assembled polymeric nanoparticles [43] or QDs
[44] to investigate targeted imaging and delivery.
12 Click Chemistry for Radionanomedicine Platform
237
Also, there are huge varieties of macromolecules which can target the specific
disease or diseased site. Any kinds of macromolecules with 3D structures that can
interact with target proteins, including antibody or its fragments, protein, affibody
® ,
nucleic acid, nucleic acid aptamer, and peptide aptamer, can be used or developed
as a targeting ligand molecule for nanomedicine.
First famous targeting molecules are the antibodies and their fragments. The
antibody has two epitope binding sites in a single molecule and offers an exceedingly high selectivity and binding affinity for the target proteins of interest. Several
antibodies are used in clinic by approval of FDA. Hadjipanayis et al. [37] employed
an antibody against epidermal growth factor receptor (EGFR) deletion mutant to
fabricate iron oxide nanoparticles for targeted imaging and therapeutic treatment of
glioblastoma. Selective binding to this mutant EGFR was achieved by creating a
polyclonal rabbit antibody toward the chemically synthesized 14-amino-acid fusion
junction sequence (EGFRvIIIAb). Covalent conjugation of the purified rabbit
polyclonal EGFRvIIIAb to the amphiphilic triblock copolymer-coated iron oxide
nanoparticles showed glioblastoma-targeting ability as a potential theranostic agent.
Even though the well-established targeting ability and selectivity of antibody itself,
antibody fragment is used frequently as a targeting molecules for nanomaterials,
because of the relatively large size of antibody with 10–15 nm (150 kDa) compared
to nanomaterials. Ling et al. reported iron oxide nanoparticles with the single chain
anti-prostate stem cell antigen (PSCA) antibody fragment (scAbP-SCA) as a
specific targeting molecule for prostate cancer targeted imaging and therapy [38]. In
a similar way, Chen et al. constructed iron oxide and non-viral polymeric vector
nanocomposite using a CD3 single chain antibody (scAbCD3) as a targeting
molecules for gene delivery to T cells [39]. Antibody-conjugated liposomes, so
called immunoliposomes, are common pharmaceutical carriers for targeted drug
delivery because of their unique ability to encapsulate both hydrophilic and
hydrophobic therapeutic agents. Lu et al. developed in vivo lung cancer targeting
immunoliposomes using an anti-c-Met single chain variable fragment (scFv) antibody [40].
Aptamers are small nucleic acid ligands (15–40 bases) and used as targeting
molecules that bind to targets with high specificity due to the ability of the molecules to fold into unique conformations with three-dimensional structures [41].
Aptamers have potential advantage over antibodies, such as the small size
(15 kDa), low immunogenicity, and easy scale-up preparation without
batch-to-batch variations. Lupold et al. identified 2′-fluoro-pyridine-RNA aptamers
generated against the extracellular domain of prostate-specific membrane antigen
(PSMA) [42] and attached on self-assembled polymeric nanoparticles [43] or QDs
[44] to investigate targeted imaging and delivery.
12 Click Chemistry for Radionanomedicine Platform
237