Biomaterial-Based Particulate Drug Carriers - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 9

including conformational-selective ones, are a wide class of targeting
agents, perhaps the most investigated [1-3, 16-20, 28]. Key examples
of other extensively investigated targeting agents include LDL, EGF,
transferrin, folate, biological haptens, and hyaluronan [2, 29-36].
Additional biologically derived targeting ligands are exemplified
by collagen-originating RGD peptides [37-38]. The specificity of
bio-originating targeting agents to their respective receptors are
clear and well-documented [2, 29-38]. A receptor that nature has
developed for a given ligand — serving as a targeting agent — binds
that ligand with high affinity and binds other molecules, even if quite
similar, with low affinity or none. The dual role biological targets can
play in biomaterial-based drug carriers is to serve as both a carrier
component and a targeting agent. This dual role is exemplified by
two systems developed in our group: gagomers, in which hyaluronan
is both the shell of the particulate carrier and a targeting agent [13,
15, 39]; collagomers, in which collagen is both a particle component
and a targeting agent [12].
The other side of the coin, receptor target-uniqueness is not
as achievable as receptor-targeter specificity. For the most, as
exemplified by several following examples, such uniqueness is a
quantitative, rather than a qualitative, matter [2, 29-38]. On its face
— a membrane-embedded antigen could be considered to also have
qualitative target uniqueness. The reality is, however, that mAbs
raised against such an antigen may still bind with sufficient affinity
to other binding entities, turning the antigen case from qualitative
to quantitative, and requiring a case-by-case analysis to evaluate
the level of target-uniqueness. As targeters, mAb have other issues
that will be discussed in a later chapter. For carrier-mediated cancer
therapy, hyaluronan receptors harbored by cell membranes — in
particular, the CD44 family and — CD168 are an example of highly
quantitative target uniqueness, supported by experimental evidence
[2, 13, 15, 30-31, 40 and references within]: In many types of tumor
cells, there is overexpression of HA membrane-embedded receptors
that are furthermore in an active conformation for high-affinity
hyaluronan binding, whereas in most normal cells, these receptors
are poorly expressed and in a conformation inactive for HA binding
[2, 13, 15, 30-31, 40 and references within]. On the other hand,
for carrier-mediated cancer therapy, cell membrane-embedded
receptors for RGD peptides and (separately) for LDL, are examples
of insufficient quantitative target uniqueness. The diff erences in