q 2006 by Taylor & Francis Group, LLC - Developers

Active Targeting Strategies in Cancer with a Focus on Potential Nanotechnology Applications 27
well as nanoparticle size for some routes of administration. Recent studies have called into question
the safety of repeated aerosolized exposure of carbon nanomaterials, 66 and nanoparticles have been
shown to have a higher inflammatory potential per given mass than do larger particles. 57 Such
particles may provide an efficient means to actively target lung cancers that is facilitated by the
natural properties of these materials. In general, safety issues related to using nanoparticles to target
cancers for treatment and diagnosis will be specific for the material used to prepare the particle: its
size, the type of targeting mechanism it utilizes, its fate at the targeted site, and its non-targeted
distribution and elimination pattern from the body.
3.4 TARGETING TO CANCER CELLS
In a very simplified sense, cancers occur through dysregulation of normal cell function. The body is
designed to correct tissue defects following damage, to expand selected immune cells in response to
a pathogen, and to compensate for perceived deficiencies in one cell type by altering the phenotype
of another such as in stem cell recruitment. Each of these processes is mediated by (normally)
regulated events that allow cells to lose their differentiated phenotype with restrained growth
characteristics and acquire a replication-driven phenotype. A lack of re-differentiation into a
growth-restrained, differentiated phenotype is the paradigm of cancer. Repair of an epithelial
wound is a good example of this phenomenon (Figure 3.3). It is the lack of re-differentiation
and continued responsiveness of these cells to growth factors and growth activators that supports
and maintains the cancer phenotype. Extensive genomic differences between differentiated and
non-differentiated forms of the same cell account for the differences observed between these two
cell phenotypes. 67
(a)
(b)
(c)
(d)
Growth
factors
Cell division
FIGURE 3.3 Loss and recovery of barrier function associated with normal epithelia. (a) Epithelia express tight
junctions ( ) and associate at their base with a complex of proteins known as the basement membrane
( ). (b) Damage to epithelia increases responses to growth factors and results in differentiated epithelial
cells that can freely divide. (c) Cell division continues until damaged area is covered. (d) Cell–cell contacts
such as adherens junctions, tight junctions, and gap junctions have been shown to suppress growth and
stimulate re-differentiation.
q 2006 by Taylor & Francis Group, LLC