Biomedical Engineering Reference
In-Depth Information
(~ 2.0-40.0 μM) [2, 3]. Furthermore, the GSH concentration in some can-
cer cells (e.g., A549 cells, a human lung adenocarcinoma cell line) has been
reported to be several times higher than that in normal cells [3].
Apart from the stimuli-responsive properties, excellent biocompatibility
and appropriate biodegradability are the other requirements for ideal nano-
carriers in practical applications [24]. Polypeptides, which are poly(amino
acid)s linked by amide bonds, are some of the most potentially biocompat-
ible and biodegradable synthetic polymers with mimicking structures of
natural proteins, and have been widely used in various biomedical realms
including drug and gene delivery, biosensors and diagnostics, etc. [25, 26].
Compared with the conventional biomaterials, polypeptides may form
stable secondary structures, such as α-helix and β-sheet, attributed to the
cooperative hydrogen-bonding [27]. Furthermore, the self-assemblies of
polypeptides exhibit smart response to dif erent external environmental
stimuli, especially pH and reduction [17, 28]. h erefore, the smart poly-
peptide nanocarriers have attracted increasing attention for their great
potential in controlled antitumor drug delivery. h is chapter focuses on
the recent progress in stimuli-responsive polypeptide nanovehicles, par-
ticularly pH and/or reduction-responsive ones, which have been exploited
as nanocarriers for antitumor drugs.
15.2
Smart Polypeptide Nanovehicles for Antitumor
Drug Delivery
15.2.1 Polypeptide Micelles
h e polymeric micelles are nanosized colloids that are spontaneously self-
assembled from amphiphilic copolymers in aqueous environment driven
by microphase separation [29-32]. h e micelles exhibit a hydrophobic core
commonly composed of hydrophobic segments (e.g., polypeptides), which
are shielded by a nonfouling hydrophilic shell (e.g., poly(ethylene glycol)
(PEG)) [33-36]. h e hydrophobic cores serve as the sustained release
reservoirs of bioactive molecules, especially antitumor drugs, while the
hydrophilic shells improve the stabilities and compatibilities of micelles
in sophisticated
in vivo
circulatory systems [33, 35, 36]. In addition, the
appropriate nanoscales of micelles (~10-200 nm) endow them with posi-
tive targeting function ascribed to their enhanced permeation and reten-
tion ef ect [17, 24, 37, 38]. As a result, polymeric micelles have attracted
signii cant attention as drug delivery platforms for malignancy thera-
peutics. Among them, the micelles originating from stimuli-responsive
