Biomedical Engineering Reference
In-Depth Information
doxorubicin (DOX), paclitaxel, chlorambucil, platinum drugs,
et al.
[4-7],
the clinical ef ects are disappointing because of some serious impediments,
such as severe side ef ects to normal tissues and low ei cacy towards mul-
tidrug-resistant tumor cells. In order to overcome the aforementioned
adverse reactions, various nanocarriers, that is, micelles, vesicles, nanogels
and so on, have been explosively exploited as nanovehicles for antitumor
drug delivery [8-12].
Among all of the aforementioned nanovehicles, the smart ones that
sharply respond to the external environmental stimuli including pH,
reduction, temperature, enzyme and light, as well as electromagnetic
i eld, have received extensive attention for their unique advantages in the
i eld of controlled transportation of antitumor drugs [13-16]. h e “on-
demand” release of payloads from the intelligent delivery systems can be
triggered by the stimuli of microenvironments in the pathological sites,
resulting in an enhanced inhibition ei cacy to tumor cellular proliferation
with reduced side ef ects [17, 18]. Given the specii c chemical microenvi-
ronments in tumor tissues and cells, the nanocarriers responding to pH
and/or reduction exhibit great potential in smart antitumor drug delivery.
In detail, the pH values in late endosome (pH ~ 5.0-6.0) and lysosome
(pH ~ 4.5-5.0) (Table 15.1) are remarkably lower than the extracellular
pH (pH ~ 6.5-7.4) [19-22]. Additionally, the reduction-responsive link-
ers (e.g., disuli de and diselenide bonds) are stable at normal physiological
condition, but degrade to free thiols or selenols in the presence of gluta-
thione (GSH) or reductases [2, 3, 23]. h e intracellular concentration of
GSH (~ 0.5-10.0 mM) is signii cantly higher than that of outside cells
Table 15.1
h e pH values in normal and tumor tissues and
cellular compartments [19-22].
Tissue or cellular compartment
pH
Normal tissue
7.4
Tumor tissue
6.5 - 7.2
Circulatory system
7.35 - 7.45
Early endosome
6.0 - 6.5
Late endosome
5.0 - 6.0
Lysosome
4.5 - 5.0
