Novel DNA-gated mesoporous silica nanoparticle (MSN) vehicles functionalized with disulfide-linked acridinamine intercalators are constructed for multi-responsive controlled release. The DNA-gated MSN vehicles release cargo encapsulated in the MSN pores under different stimuli, including disulfide reducing agents, elevated temperature, and deoxyribonuclease I (DNase I), for codelivery of drugs and DNA/genes in different forms. Furthermore, the cascade release of encapsulated and intercalative drugs is controlled by AND logic gates in combination of dual stimuli. The ingeniously designed DNA-gated MSN vehicles integrates multiple responses and AND logic gate operations into a single smart nanodevice not only for codelivery of drugs and DNA/genes but also for cascade release of two drugs and has promising biological applications to meet diverse requirements of controlled release.
An integrated γ-cyclodextrin-gated mesoporous silica delivery system via dual dynamic covalent bonds was constructed with dual drug loading for simultaneous and cascade release in targeted combination drug therapy.
Stimuli-responsive multidrug delivery systems need to be invented for clinical combination therapy by the controlled release behavior of each drug individually. A facile, effective, and universal platform was built for simultaneous and cascade release of two drugs from DNA-gated gold nanorod-embedded mesoporous silica nanoparticles (MSNs) functionalized with titanium(IV)-chelating phosphonates. Coordination chemistry is the first strategy for DNA capping through multivalent chelating interactions in drug delivery systems not only as a gatekeeper but also as a drug carrier. One drug was entrapped in the MSN pores, and the other drug intercalated within the capping duplex DNA. The two drugs were simultaneously released upon triggering of endonuclease degradation or photothermal dehybridization and were successively released upon first triggering of basic pH and subsequent triggering of photothermal heating. The designed native DNA-gated MSN delivery systems integrated a simultaneous and cascade release of two drugs into smart single nanovehicles for promising practical applications in targeted combination drug therapy.XRD, nitrogen adsorption-desorption isotherms and pore size distributions, thermogravimetric analysis, zeta potentials, hydrodynamic diameters, FTIR, UV-vis, and uorescence spectra, 13 C NMR spectral assignments, stimuli-responsive time-dependent uorescence spectra and release proles, GNR-generating photothermal heating, cell viability, and CLSM images. See
Iron
oxide nanoparticles can induce cell death due to the ferroptosis
mechanism, showing a great potential for cancer therapy. Here, we
synthesized different-sized iron oxide nanoparticles (2–100
nm) to investigate their antitumor effect and toxicity mechanism.
It was found that ultrasmall nanoparticles (< ∼5 nm) could
accumulate in nucleus and were more efficient in triggering the generation
of •OH than larger nanoparticles due to the quicker
release of Fe2+, thus exhibiting more remarkable cytotoxicity.
Nevertheless, 10 nm iron oxide nanoparticles group displayed the best
antitumor effect in vivo. We studied the in vivo and intratumoral biodistribution of the nanoparticles
and found that the therapeutic effects were related to both the tumoral
accumulation and intratumoral distribution of nanoparticles. This
work indicates the appropriate size of Fe3O4 NPs for cancer treatment and illustrates the possible factors that
influence the therapeutic effect, suggesting the great potential of
iron oxide in clinical application.
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