fragments without a human host, and the generation of entirely new and clinically
relevant antibodies without immunization have been studied. Antibody molecules
have been used to target NPs; however, relatively large size (approximately 12 nm)
and Fc region immunogenicity of antibody molecules necessitate the utilization of
antibody fragments rather than intact antibody molecules.
22.2.2.2 Antibody Fragments
Antibodies are about 150 kDa in size, so they clear slowly from the blood pool.
This characteristics lead to significant accumulation of antibody molecules in
normal organs and restrict their conveyance to target lesions [26]. The effective
penetration of monoclonal antibodies (mAbs) into a bulky solid tumor is rarely
reported [27]. The utilization of the antibody fragments could improve their entry to
target area. And single-chain fragments (scFvs) could not activate immune function.
Intact IgG molecules have two Fv chains, whereas scFvs have only one single
binding area; thus, binding affinity of scFvs is less than intact IgG molecules.
Compared to divalent IgG molecules, scFvs with faster clearance and lower affinity
can result in there being a lower effective dose at the target site; it should be
compensated by using a higher signal production in the functional site. Because
scFvs generated by phage display can be engineered to function without inducing
an immune response, it is likely that they will be utilized in the future to lead NPs to
the targets.
22.2.2.3 Oligonucleotides (Aptamers)
Aptamers are oligonucleotide or peptide molecules with molecular weights about
5–10 kDa that can act as ligands that bind to proteins [28] or small molecules
including metabolites [29]. They can be screened rapidly and efficiently to select the
sequences that are optimal for binding to a specific target [30]. In addition, aptamers
can recognize single protein in complex compound that are originated from cells.
[31]. Therefore, they are excellent for both cancer research and therapy [32] and
cardiovascular research and therapy [33]. Their advantages as targeting agents
include inexpensiveness and rapid synthesis with homogeneity. Aptamers are also
secure for long-term storage at room temperature. Unlike peptides, their conjugation chemistry can be simplified via hybridization or co-synthesis, and unlike lipids,
they can target specific cell types [34]. Furthermore, low molecular weights of
aptamers promote their entry to cells. Since they are tiny, they should be attached to
NPs with sufficiently long linkers to ensure that their interactions with their specific
targets are not sterically hindered.
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Y. Kim and D. S. Lee
relevant antibodies without immunization have been studied. Antibody molecules
have been used to target NPs; however, relatively large size (approximately 12 nm)
and Fc region immunogenicity of antibody molecules necessitate the utilization of
antibody fragments rather than intact antibody molecules.
22.2.2.2 Antibody Fragments
Antibodies are about 150 kDa in size, so they clear slowly from the blood pool.
This characteristics lead to significant accumulation of antibody molecules in
normal organs and restrict their conveyance to target lesions [26]. The effective
penetration of monoclonal antibodies (mAbs) into a bulky solid tumor is rarely
reported [27]. The utilization of the antibody fragments could improve their entry to
target area. And single-chain fragments (scFvs) could not activate immune function.
Intact IgG molecules have two Fv chains, whereas scFvs have only one single
binding area; thus, binding affinity of scFvs is less than intact IgG molecules.
Compared to divalent IgG molecules, scFvs with faster clearance and lower affinity
can result in there being a lower effective dose at the target site; it should be
compensated by using a higher signal production in the functional site. Because
scFvs generated by phage display can be engineered to function without inducing
an immune response, it is likely that they will be utilized in the future to lead NPs to
the targets.
22.2.2.3 Oligonucleotides (Aptamers)
Aptamers are oligonucleotide or peptide molecules with molecular weights about
5–10 kDa that can act as ligands that bind to proteins [28] or small molecules
including metabolites [29]. They can be screened rapidly and efficiently to select the
sequences that are optimal for binding to a specific target [30]. In addition, aptamers
can recognize single protein in complex compound that are originated from cells.
[31]. Therefore, they are excellent for both cancer research and therapy [32] and
cardiovascular research and therapy [33]. Their advantages as targeting agents
include inexpensiveness and rapid synthesis with homogeneity. Aptamers are also
secure for long-term storage at room temperature. Unlike peptides, their conjugation chemistry can be simplified via hybridization or co-synthesis, and unlike lipids,
they can target specific cell types [34]. Furthermore, low molecular weights of
aptamers promote their entry to cells. Since they are tiny, they should be attached to
NPs with sufficiently long linkers to ensure that their interactions with their specific
targets are not sterically hindered.
416
Y. Kim and D. S. Lee