Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 30, Pages 35397-35409Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c08532
Keywords
chiral mesoporous silica nanorods; pH/H2O2 dual responsiveness; active targeting therapy; supramolecular switches; biosafety
Funding
- National Natural Science Foundation of China [81773672, 81903550]
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This study successfully constructed chiral mesoporous silica nanorods with pH/H2O2 dual-responsiveness, enabling intelligent drug delivery and increased drug accumulation in tumor regions. The combination of mesoporous structure and supramolecular switch provided effective drug release mechanisms in response to the tumor microenvironment.
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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