Metal−organic frameworks (MOFs) have received extensive attention in the field of biomedicine, particularly serving as multifunctional theranostic nanoplatforms by integrating chemodrugs, imaging agents, and targeting agents. Herein, we report a facile strategy for the fabrication of a hollow and monodisperse MOF (denoted hMIL-88B(Fe)@ZIF-8) consisting of ZIF-8 nanoparticles loaded on the external shell of hollow MIL-88B(Fe). In particular, the hybrid hollow MOF was constructed by partially etching spindlelike MIL-88B(Fe) nanoparticles with 2methylimidazole in the presence of zinc ions. The obtained hMIL-88B(Fe)@ZIF-8 was then used as a drug/cargo delivery vehicle for loading doxorubicin (DOX), manganese oxide (MnO x ) nanoparticles, and folic acid (FA), forming a multifunctional nanoplatform (denoted hM@ZMDF). Importantly, the resulting hM@ZMDF exhibited a specific targeting property for the FA receptor-overexpressed cancer cells (MCF-7 and HepG-2 cells) and then it unloaded DOX and Fe 3+ in the tumor microenvironment. Consequently, DOX played dual roles as a chemotherapeutic drug and a fluorescent imaging agent. Also, the released Fe 3+ could mediate the Fenton reaction and intracellularly generate toxic hydroxyl radicals in the presence of high glutathione in cancer cells. In addition, MnO x nanoparticles could participate in magnetic resonance imaging. Therefore, the versatile hM@ZMDF nanoplatforms have great potential for smart cancer therapy.
An ortho-ester-linked
indomethacin (IND) dimer-based nanodrug delivery
system was prepared to improve the therapeutic effect of doxorubicin
(DOX) by reversing the multidrug resistance. The synthesized dimer
(IND-OE) could form stable nanoparticles (IND-OE/DOX) loaded with
DOX via the single-emulsion method. Compare to insensitive nanoparticles
(IND-C12/DOX), IND-OE/DOX showed a rapid degradation behavior and
accelerated drug release at mildly acidic environments. In vitro cell
experiments verified that IND-OE nanoparticles could increase DOX
concentration due to the efficient intracellular drug release by the
degradation of the ortho ester as well as reduced DOX efflux by IND-mediated
P-gp downregulation. In vivo studies further demonstrated that IND-OE/DOX
displayed the maximized synergetic antitumor efficacy than free DOX
or IND-C12/DOX, and the tumor inhibition rates versus saline were
46.78% (free DOX), 60.23% (IND-C12/DOX), and 80.62% (IND-OE/DOX).
Overall, this strategy of combination with chemosensitizers and ortho
ester linkage has great potential to serve as an amplifying chemotherapy
platform against various drug-resistant tumors.
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