Biomedical Engineering Reference
In-Depth Information
15.2.3.2
Reduction-Responsive Polypeptide Nanogels
As the pH-responsive polypeptide nanogels, the reduction-responsive
polypeptide nanogels are another potential intracellular drug delivery sys-
tem that benei t from the obvious dif erent GSH level outside and inside
cells. Jing and coworkers have developed the reversible nanogel through
the shell crosslinking of poly(L-cysteine)-
b
-poly(L-lactide) micelle [72].
h e diameter of nanogel was reduction-dependent, which increased
slightly from 41.7 to 55.1 nm at er the addition of DTT, while it decreased
to 47.1 nm at er the removal of DTT. Rifampin, as a hydrophobic model
drug, was loaded into nanogel via the self-assembly of copolymer and
drug, and followed aerial oxidation with DLE at 17.5 wt%. In comparison
to its parent micelle, the rifampin-loaded nanogel with a larger diameter
(
65 nm) showed faster drug release in the presence of DTT ascribed to
the decrosslinking of nanogels induced by the DTT-induced cleavage of
disuli de bond.
More meaningfully, the disuli de-core-crosslinked nanogels based on
polypeptides have been independently developed by a facile one-step ring-
opening polymerization (ROP) technique by the groups of Chen and Yan
[73, 74]. In two separate studies, a difunctional
N
-carboxyanhydride (i.e.,
L-cystine NCA (LC NCA)) was synthesized. h e reduction-responsive
nanogels were fabricated through the copolymerization of LC NCA indi-
vidually or together with other NCA monomers (e.g., L-phenylalanine (LP)
NCA and γ-benzyl-L-glutamate (BLG) NCA). As a model antitumor drug,
DOX was loaded into mPEG-P(LC-
co
-LP) nanogels through the dif usion
approach [73]. More than 90 wt% of loaded DOX was released from nano-
gels at 93.5 h in the presence of 10.0 mM GSH, while only less than 20 wt%
of loaded DOX was released in PBS without GSH. Additionally, a faster
DOX release was observed from the drug-loaded nanogels with lower con-
tent of LC or overall polypeptides. Furthermore, the DOX-loaded nanogel
exhibited enhanced intracellular drug release and antiproliferative activ-
ity toward GSH-pretreated HeLa cells. Similarly, a GSH-mediated indo-
metacin release from a PEG-P(LC-
co
-BLG) nanogel was coni rmed by
Yan and coworkers [74]. In addition, the near-infrared cyanine dye modi-
i ed reduction-responsive polypeptide nanogels were further exploited as
directly imaged intracellular antitumor drug carrier in Yan's group [75, 76].
With convenient fabrication, excellent stability in the circulation systems,
accelerated intracellular drug release and potential modii cation, the above
polypeptide nanogels hold great prospects for chemotherapy in malig-
nancy therapeutics.
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