Recent Progress in Polymer Therapeutics as Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 90

Since angiogenesis was recognized as a significant process in the
formation and progression of tumors, the objective of targeting toxic
agents to the endothelial cells in the tumor microvasculature, rather
than the tumor cells, became established. This approach presents
mainly three advantages: First, killing proliferating TEC in the tumor
microenvironment can be eff ective against a variety of malignancies,
since the therapeutic target is not subjected to a tumor type. Second,
anti-angiogenic therapy is considered to be relatively genetically
stable and thus possesses the potential to avoid the development
of drug resistance. Third, since cancer cells depend on TEC for
survival and growth, this strategy may amplify the anti-angiogenic
therapeutic eff ect. However, this approach still presents an indirect
killing of tumor cells. Anti-angiogenic therapy is aimed to cause delay
of tumor growth and stabilize the cancer disease. In this approach,
limited eradication of tumor cells will be obtained. In addition, since
usually lower concentration of the drug is being used, the duration
of the treatment will be longer. But, it is important to note that fewer
side eff ects will be expected from the same reason. Representative
examples of molecular markers of the angiogenic blood vessels of
tumors are presented in Figure 4.2 and listed in Table 4.2.
4.2 PolymericDrugs
Unlike polymer-protein and polymer-drug conjugates, examples of
intrinsically bioactive polymers are relatively scarce [78]. However,
a careful examination of the characteristics of polymers reveals that
they off er a number of features that are not present in traditional
small molecule therapies. For examples, when ingested orally, high
Mw characteristics of polymers limit their absorption through the
gastrointestinal (GI) tract. In this way, we can limit these functional
polymers to the GI or other areas and avoid systemic exposure.
Furthermore, polymeric drugs as active pharmaceutical ingredients
off er more simplicity, since the polymer itself serves as the drug and
complicated synthesis of polymer conjugates is avoided. Finally, the
ability to incorporate a variety of binding sites and large amount of
ligands along the polymer chain can lead to multivalent interaction
with target ligands and thus off ers higher binding constant than with
smaller molecular weight drugs.
A wide range of novel functional polymers have been synthesized
during the last three decades, in which the role of polymers in