Biomedical Engineering Reference
In-Depth Information
respond to a tiny variation in environmental conditions, with subsequent
obvious alteration in some aspect like shape, volume, phase state, or electrical,
optical, mechanical, or surface properties. Therefore, HBPs with responsive-
ness are widely exploited to improve the functionality of delivery. In this
section, we focus on stimuli-responsive HBPs which are sensitive to pH,
temperature, and reduction, respectively.
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5.3.1.1 pH Responsiveness
As we know, most tumor cells have an elevated acid level. In tumor tissue,
extracellular pH (pH
e
#
6.8) is slightly more acidic than the pH in normal
tissue (pH
#
7.4), mainly due to the anaerobic respiration and subsequent
glycolysis together with the tumor phenotype. In the organelles, such as the
endosome or lysosome (pH
endo
#
5.0), the acid level is further increased,
promoting drug or gene release from the endocytosed nanocarriers.
33
Therefore, the pH-sensitive polymeric self-assemblies which can rapidly
respond to the mild acidic pH trigger provide an opportunity for the
achievement of programmable and controlled drug delivery. Up to now, a
series of acid-cleavable covalent linkages have been designed and applied in
polymeric carriers to obtain pH-sensitive materials. Introducing pH-sensitive
moieties into HBPs endows them with responsive functions. For example, the
ionizable moieties (carbonyl and amine groups, etc.) and acid-cleavable
covalent bonds (acetal, orthoester, and cis-acotinyl, etc.) render HBPs pH
responsive. On the one hand, driven by the electrostatic and hydrogen bonding
interactions, the protonation of HBPs directly leads to a change of the electric
charge, ionic polarity, solubility, and even the whole chemical environment of
HBPs, which reflects the pH-dependent manner of the smart materials. On the
other hand, the acid-sensitive covalent bonds, including dynamic covalent
bonds
(hydrazone,
imine,
and
oxime
bonds),
can
reversibly
react
with
hydrogen ions, resulting in changes of the chemical properties of HBPs.
According to our work published previously, hyperbranched poly[3-methyl-
3- (hydroxymethyl)oxetane] (HPMHO) was prepared. Subsequently, succinic
anhydride (SA) was tethered onto HPMHO by Xia et al., thus obtaining
carboxyl-modified HPMHOs with different carboxyl terminal contents (Suc-
HPMHOs) through esterification of HPMHO and SA.
34
Because of the
existence of the hydrophobic core and hydrophilic ionization of the carboxylic
acid at the periphery, the HBP could homogenously disperse in water. The pH-
responsive range of these Suc-HPMHOs can be easily adjusted by controlling
the degree of carboxylation, involving the extracellular pH (pH
e
#
6.8).
Terminal
modification
of
HPMHO
allows
the
carboxyl
groups
to
bind
cisplatin
through
electrostatic
interaction,
constructing
a
HBP-cisplatin
complex for antitumor investigation.
The pH-labile linkages endow HBPs with the function of pH responsiveness,
and realize the programmable release of drug or gene according to the
environmental pH alteration. For instance, Zhu et al. prepared a pH-sensitive
