This phenomenon was termed "binding site barrier" (Fujimori et al., 1990).
These results indicate that solid tissues are more difficult to penetrate by mAb and the "binding site barrier" could restrict the distribution of mAb, leading to a delayed pharmacological effect in the tissues.
It has been shown that high-affinity radioimmunoconjugates (low K D values) generally have low penetration and reduced diffusion due to the so-called binding site barrier [35], known to limit therapeutic efficacy.
The radical C2 prefers to graft in sp3 carbon skeletons in the low binding energy barrier (~6 kcal/mol), which indicate the process does not need open site or dangling bond from H atom bombardment [33].
Using mAbs that recognize the same Her2 epitope but with different affinities (270, 23, 7.3, and 0.56 nmol/L), Rudnick et al. confirmed the "binding site barrier" phenomenon in vivo.
For the specific case of shedded antigens and high-affinity binders, Pak et al. has suggested that this combination might circumvent the binding site barrier issues seen with high-affinity binders [37].
In addition, diffusion of IgG from well perfused tumor regions may also be limited by a binding site barrier [29].
The ability of the DNA binding protein Barrier to Autointegration Factor (BAF) to inhibit replication of VACV B1 kinase mutants provides a model for such an activity [50].
However, surface interactions of cationic liposomes with the tumor cells produce an electrostatically derived binding site barrier effect, inhibiting further association of the delivery systems with tumor spheroids [ 22].
If C225-HAuNS shows significantly greater receptor-binding avidity than apt-HAuNS, it is possible that the "binding site barrier effect" may play a role in restricting tumor penetration of C225-HAuNS as compared to apt-HAuNS, much like what is observed with monoclonal antibodies of different binding affinity.
