Nano-drug delivery systems (nano-DDSs)
with an existing specific
interaction to tumor cells and intelligent stimulus-triggered drug
delivery performance in a tumor microenvironment (TME) remain hotspots
for effective cancer therapy. Herein, multifunctional pH/H2O2 dual-responsive chiral mesoporous silica nanorods (HA-CD/DOX-PCMSRs)
were creatively constructed by first grafting phenylboronic acid pinacol
ester (PBAP) onto the amino-functioned nanorods, then incorporating
doxorubicin (DOX) into the mesoporous structure, and finally coating
with the cyclodextrin-modified hyaluronic acid conjugate (HA-CD) through
a weak host–guest interaction. Under a physiological environment,
the gatekeeper CD could avoid the premature leakage of DOX and minimize
the side effects to normal cells. After the uptake by the tumor cells,
the H2O2-sensitive moieties of PBAP were exposed
and a small amount of DOX was leaked along with the shift of the supramolecular
switch HA-CD under the acidic condition. Notably, the self-supplying
H2O2 mediated by the released DOX in turn accelerated
the PBAP disintegration, further promoted the rapid release of DOX,
and increased the DOX accumulation in tumor regions. Innovatively,
this nano-DDS could simultaneously achieve the tumor-targeting ability
via CD44 receptor-mediated endocytosis and pH/H2O2 dual responsiveness activated by the TME and hence exhibited superior
antitumor efficacy. Furthermore, HA acting as the hydrophilic shell
could improve the biocompatibility of this nano-DDS.
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