Protein-Gated Upconversion Nanoparticle-Embedded Mesoporous Silica Nanovehicles via Diselenide Linkages for Drug Release Tracking in Real Time and Tumor Chemotherapy

Abstract

Two novel stimuli-responsive drug delivery systems (DDSs) were successfully created from bovine serum albumin- or myoglobin-gated upconversion nanoparticle-embedded mesoporous silica nanovehicles (UCNP@mSiO2) via diselenide (Se–Se)-containing linkages. More importantly, multiple roles of each scaffold of the nanovehicles were achieved. The controlled release of the encapsulated drug doxorubicin (DOX) within the mesopores was activated by triple stimuli (acidic pH, glutathione, or H2O2) of tumor microenvironments, owing to the conformation/surface charge changes in proteins or the reductive/oxidative cleavages of the Se–Se bonds. Upon release of DOX, the Förster resonance energy transfer between the UCNP cores and encapsulated DOX was eliminated, resulting in an increase in ratiometric upconversion luminescence for DOX release tracking in real time. The two protein-gated DDSs showed some differences in the drug release performances, relevant to structures and properties of the protein nanogates. The introduction of the Se–Se linkages not only increased the versatility of reductive/oxidative cleavages but also showed less cytotoxicity to all cell lines. The DOX-loaded protein-gated nanovehicles showed the inhibitory effect on tumor growth in tumor-bearing mice and negligible damage/toxicity to the normal tissues. The constructed nanovehicles in a spatiotemporally controlled manner have fascinating prospects in targeted drug delivery for cancer chemotherapy.

Nanoarchitectured prototypes of mesoporous silica nanoparticles for innovative biomedical applications

“…Apart from a single trigger, several studies have explored the utilization of multiple stimuli (two or more) either to control the release of therapeutic guests by unlocking the capping or the conveyance of the MSNs [ 297 ]. In this regard, various multiple stimuli combinations employed in the fabrication of advanced prototypes of MSNs include pH, GSH, or H 2 O 2 -responsive [ 298 ], redox-enhanced pH-responsive [ 297 , 299 ], thermos- and pH-responsive [ 261 ], pH- and GSH-responsive [ 300 , 301 ], GSH- and NIR-triggered [ 302 ] nanocomposites. These composites with multiple stimuli-triggered delivery or degradation offer more advantages than the single stimuli-based composites.…”

Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

“…The most extended strategy for designing redox-responsive MSNs involves grafting the different gatekeepers to the surface using redox-responsive linkers. For instance, albumin or myoglobin can be employed to prevent premature drug release by attaching them to the MSNs using diselenide bonds, obtaining a nanocarrier highly responsive to both GSH and H 2 O 2 [21]. Rather than using bulky proteins, the use of small peptidic molecules as gatekeepers has also been reported.…”

On-Demand Drug-Delivery Platform Using Electrospun Nanofibers by Externally Triggered Glass Transition Switch

“…The development of on-demand drug release methods from polymer matrices has recently gained considerable attention. By making drug stimuli dependent, on-demand drug-delivery systems (DDSs) can explicitly control where, when, and how much of a drug is released with controlled release profiles and minimal off-target effects. , Various stimuli such as temperature, light, biomarkers, pH, magnetic field, electric field, and ultrasound have been used (alone or in combination) in on-demand DDSs. − The majority of conventional DDSs involve enteral routes, such as granules, capsules, and pills, while others involve parenteral delivery methods, such as subcutaneous, intramuscular, intravenous, or intra-arterial injection. − The routes and methods of administration have several disadvantages, including first-pass metabolism and discomfort. − Therefore, the development of a novel drug-delivery system is essential because it enables targeted drug administration while maintaining sustained and controlled release of drug throughout the treatment process.…”