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In-Depth Information
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(a)
(b)
FIGURE 11.2
The early identification of breast cancer bone metastasis lesion by NIR dye-
labeled osteotropic polyrotaxane. (a) Luciferase activity associated with breast cancer cells
was mainly found at knee joints (bone metastatic sites) and heart (due to intracardial injection
of Luciferase-expressing breast cancer cells); (b) High signal intensity of NIR-dye-labeled
osteotropic polyrotaxane was found at knee joints but not the heart, which identifies these
positions as cancer bone metastasis. (See color plate section.)
increase the osteotropicity of the polymer conjugates. When tested in a spontaneous
breast cancer bone metastasis model, the team observed that the near-infrared (NIR)
dye-labeled osteotropic polyrotaxane could discover micrometastasis sites, which are
invisible to
-CT scan (Figure 11.2). This was confirmed by the presence of GFP
+
breast cancer cells at the metastasis sites. This observation may be attributed to the
leaky vasculature associated with micrometastatic lesion, which allows the polymeric
conjugates' site-specific extravasation and the freshly eroded local bone surface that
favors the binding to the lesion. An osteotropic docetaxol polyrotaxane conjugate has
been synthesized and it is currently under evaluation for the improved treatment of
breast cancer bone metastasis.
11.4 SUMMARY
In this chapter, we have presented some of the most exciting recent developments
of CDs and their various biomedical applications. Often, these transforming devel-
opments are natural extensions from the previous work, which was not possible in
the past. The introduction of “click” reactions revolutionized the development of
CD derivatives. Most notably, the high reaction efficiency, stereospecificity, simple
reaction conditions, and tolerance of various solvent systems make “click” reactions
excellent tools for CDs' modification. The field is still at its early stage of develop-
ment. In the next few years, we anticipate that many more exciting CDs' derivatives
will be developed and used in various biomedical applications. Due to the concern
of Cu catalyst residue in the final product, we believe Cu-free “click” HDC reaction
will be used more often, especially for products to be used
in vivo
. For the same
reason, other types of “click” reactions (e.g., Michael addition) may find use in CDs'
modifications.
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