X-ray-controllable release of carbon monoxide potentiates radiotherapy by ultrastable hybrid nanoreservoirs.

Carbon monoxide (CO) exhibits unique abilities in sensitizing cancer radiotherapy (RT). However, the development of a highly stable CO-delivery nanosystem with sustained CO release in tumor tissues and the prevention of CO leakage into normal tissues remains a challenge. Herein, an organic-inorganic hybrid strategy is proposed to create ultrastable CO nanoreservoirs by locking an unstable iron carbonyl (FeCO) prodrug in a stable mesoporous silica matrix. Different from traditional FeCO-loading nanoplatforms, FeCO-bridged nanoreservoirs not only tethered labile FeCO in the framework to prevent unwanted FeCO leakage, but also achieved sustained CO release in response to X-ray and endogenous H2O2. Importantly, FeCO-bridged nanoreservoirs exhibited the sequential release of CO and Fe2+, thereby performing highly efficient chemodynamic therapy. Such a powerful combination of RT, gas therapy, and chemodynamic therapy boosts robust immunogenic cell death, thus enabling the elimination of deeply metastatic colon tumors with minimal side effects. The proposed organic-inorganic hybrid strategy opens a new window for the development of stable nanoreservoirs for the on-demand delivery of unstable gases and provides a feasible approach for the sequential release of CO and metal ions from metal carbonyl complexes.

Designing Hybrid Mesoporous Pr/Tannate-Inbuilt ZIF8-Decorated MoS2 as Novel Nanoreservoirs toward Smart pH-Triggered Anti-corrosion/Robust Thermomechanical Epoxy Nanocoatings.

For the first time, organic tannic acid (TA) molecules and then inorganic praseodymium (Pr) cations as corrosion inhibitors were successfully loaded into a zeolitic imidazolate framework (ZIF8)-type porous coordination polymer (PCP) decorated on molybdenum disulfide, MoS2, (MS)-based transition metal dichalcogenides (TMDs) to create novel hybrid mesoporous Pr/TA-ZIF8@MS nanoreservoirs. Thereafter, the hybrid nanoreservoirs were embedded into the epoxy matrix for the preparation of smart pH-triggered nanocoatings. Characterizations of the Pr/TA-ZIF8@MS nanoreservoirs via Fourier transform infrared (FT-IR), X-ray diffraction (XRD), thermogravimetric (TG), Brunauer-Emmett-Teller (BET), and field emission-scanning electron microscopy (FE-SEM)/energy-dispersive X-ray spectroscopy (EDS) experiments confirmed the fabrication of mesoporous structures comprising Pr/TA interfacial interactions with ZIF8-decorated MS nanoplatelets possessing high thermal stability and compact/dense configuration features with a framework reorientation. A remarkable smart release of the inhibited cations (Pr3+ and Zn2+) in the presence of inbuilt TA at both acidic and alkaline media was achieved under inductively coupled plasma (ICP) examination. The superior pH-triggered self-healing inhibition through the smart controlled-release of Pr, tannate, Zn, and imidazole inhibited species/complexes from EP/Pr-TA-ZIF8@MS via ligand exchange was obtained from electrochemical impedance spectroscopy (EIS) assessments of the scratched coatings during 72 h of saline immersion. In addition, the long-term barrier-induced corrosion prevention (log |Z|10 mHz = 10.49 Ω·cm2 after 63 days) of the EP/Pr-TA-ZIF8@MS was actualized. Moreover, efficient increments of the coating cross-link density (56.45%), tensile strength (63.6%), and toughness value (56.5%) compared to the Neat epoxy coating revealed noticeable thermomechanical properties of the EP/Pr-TA-ZIF8@MS.

Nano-reservoir Bioadhesive Tablets Enhance Protein Drug Permeability Across the Small Intestine.

Most therapeutic proteins are classified as class III drugs according to the Biopharmaceutical Classification System means that the low permeability across the intestinal epithelium is the rate-limited step for their oral absorption. Cationic chitosan nanoparticles have been found to open the tight junctions between epithelial cells. On the other hand, bioadhesive delivery devices could prolong the gastrointestinal residence time. In the present study, we developed a novel nano-reservoir bioadhesive tablets that combining the advantages of cationic nanoparticles and bioadhesive delivery devices anticipated achieving effective transport of sufficient protein drugs across the intestinal epithelium. The nano-reservoir in bioadhesive tablets was composed of chitosan nanoparticles (CS-NPs) loading a model protein drug bovine serum albumin (BSA). The formula of bioadhesive tablets was optimized by using rotatable central composite design and response surface methodology. The nano-reservoir, BSA-loaded CS-NPs, had an average particle diameter of 312.5 ± 12.89 nm and zeta-potential value of 26.76 ± 3.56 mV. Carboxymethyl chitosan added to the formula significantly ameliorated the tight junction damage of the Caco-2 cell monolayer induced by CS-NPs, meanwhile maintained the high transport efficiency of BSA. Permeability study exhibited that these nano-reservoir bioadhesive tablets combining the advantages of cationic nanoparticles and bioadhesive tablets significantly enhanced BSA transport through rabbit small intestine in comparison with either conventional bioadhesive tablets or CS-NPs. Therefore, these nano-reservoir bioadhesive tablets provided a great potential dosage form design for the oral delivery of protein drugs.