A pH responsive dissociable mesoporous silica based nanoplatform enabling efficient dual drug co delivery and rapid clearance for cancer therapy.
The balance between tumor accumulation and renal clearance has severely limited the efficacy of mesoporous silica based drug nanocarriers in cancer therapy. Herein, a pH responsive dissociable mesoporous silica based nanoplatform with efficient dual drug co delivery, tumor accumulation and rapid clearance for cancer therapy is achieved by adjusting the wetting of the mesoporous silica surface. At pH 7.4, the synthesized spiropyran and fluorinated silane modified ultrasmall mesoporous silica nanoparticles (SP FS USMSN) self assemble to form larger nanoclusters (denoted as SP FS USMSN cluster) via hydrophobic interactions, which can effectively co deliver anticancer drugs, doxorubicin hydrochloride (Dox) and curcumin (Cur) based on the mesopores within SP FS USMSN and the voids among the stacked SP FS USMSN. At pH 4.5 5.5, the conformational conversion of spiropyran from a "closed" state to an "open" state causes the wetting of the SP FS USMSN surface, leading to the dissociation of the SP FS USMSN cluster for drug release and renal clearance. The in vitro and in vivo studies demonstrate that the Cur and Dox co loaded SP FS USMSN cluster (Cur Dox/SP FS USMSN cluster) possesses great combined cytotoxicity, and can accumulate into tumor tissue by its large size favored EPR effect and potently suppress tumor growth in HepG2 xenografted mice. This research demonstrates that the SP FS USMSN cluster may be a promising drug delivery system for cancer therapy and lays the foundation for practical mesoporous silica based nanomedicine designs in the future.
Biomaterials science