Biomedical Engineering Reference
In-Depth Information
Already back in the 1900s, Paul Ehrlich foresaw the concept of
the direct targeting of drugs to specific molecular cancer targets
[48]. Following his vision, active targeting combined with passive
targeting became dominant in the design of drug delivery systems.
Active targeting is expected to lead higher and faster intra-tumor
accumulation and, in the case of targeting with internalizing ligands,
to increase intracellular concentrations of the drug.
Active targeting to the tumor can be achieved by molecular
recognition of cancer cells either via ligand-receptor, antibody-
antigen interactions, or by targeting through aptamers [49]. A
successful targeting moiety should have high affinity and specificity
of binding to cell surface receptors and should be well suited
to chemical modification due to conjugation considerations.
When nanocarriers are targeted to the extracellular portion of
transmembrane tumor antigens, a diff erent mechanism of uptake
is occurred. The nanocarrier is taken up by cancer cells through
receptor-mediated endocytosis. Since the receptor is internalized
with the ligand, the system is becoming saturated and uptake will
decline until receptors are recycled to the surface.
In general, there are two approaches for targeted delivery to
cancer tissues. The first main approach is aimed to target the tumor
cells themselves. The second one utilizes the process of angiogenesis
by targeting the proliferating tumor endothelial cells (TEC). There
are several cases in which the targets are expressed at the same level
on tumor cells and normal cells (e.g., CD19) [50].
Targeting the tumor cells themselves off ers a direct killing of the
cells and thus aims to cause eradication of the tumor. Anti-cancer
therapy is basically specific to the tumor cells and is not supposed
to harm healthy tissues. In contrast, the anti-angiogenic therapy,
physiological processes of angiogenesis (e.g., wound healing,
female reproductive cycle, and organ and tissue regeneration) are
susceptible to the treatment as well. However, tumor cells suff er
from genetic instability, which leads to treatment's resistance, and
indeed this is one of the major drawbacks of targeting the tumor
cells.
Several receptors that are overexpressed in tumor cells were
used as targets in the field of polymer therapeutics and are apparent
in Figure 4.2 and listed in Table 4.2.
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