Global Gene Expression Analysis of Cellular Death Mechanisms Induced by Mesoporous Silica Nanoparticle-Based Drug Delivery System

Mesoporous silica nanoparticles (MSNs), as one of the most promising inorganic drug carriers, have attracted ever increasing attention due to their unique structural, physicochemical, and biochemical features. Drug delivery systems (DDSs) based on MSNs could easily escape from endosomes after endocytosis and protect the loaded drugs from bioerosion by stable MSN carriers, efficiently deliver drugs intracellularly in a sustained release way, and consequently kill cancer cells at enhanced efficacy. However, the underlying pathways and mechanisms of cancer cell death induced by MSN-mediated drug delivery have not been well explored. In this study, we introduce gene expression analyses to evaluate the pathways and mechanisms of cancer cell death induced by a MSN-based drug delivery system. Unique changes in gene expressions and gene ontology terms, which were caused only by the MSN-based DDS (DOX-loaded MSNs, DOX@MSNs) but not by free drug doxorubicin (DOX) and/or the carrier MSNs, were discovered and proposed to be responsible for the varied cell death mechanisms, including the greatly enhanced necrosis due to amplified oxidative stress and the apoptosis related with DNA/RNA synthesis and cell cycle inhibitions. By virtue of a certain kind of synergetic biological effect between the drug and the carrier, the DOX@MSNs DDS was found capable of increasing the intracellular levels of reactive oxygen species and triggering the mitochondria-related autophagic lysosome pathway, consequently activating a specific pathway of necrosis, which is different from those by the free drug and the carrier

Nanoenzyme-Augmented Cancer Sonodynamic Therapy by Catalytic Tumor Oxygenation

Ultrasound (US)-triggered sonodynamic therapy (SDT) can solve the critical issue of low tissue-penetrating depth of traditional phototriggered therapies, but the SDT efficacy is still not satisfactorily high in combating cancer at the current stage. Here we report on augmenting the SDT efficacy based on catalytic nanomedicine, which takes the efficient catalytic features of nanoenzymes to modulate the tumor microenvironment (TME). The multifunctional nanosonosensitizers have been successfully constructed by the integration of a MnO_<i>x</i> component with biocompatible/biodegradable hollow mesoporous organosilica nanoparticles, followed by conjugation with protoporphyrin (as the sonosensitizer) and cyclic arginine-glycine-aspartic pentapeptide (as the targeting peptide). The MnO_<i>x</i> component in the composite nanosonosensitizer acts as an inorganic nanoenzyme for converting the tumor-overexpressed hydrogen peroxide (H₂O₂) molecules into oxygen and enhancing the tumor oxygen level subsequently, which has been demonstrated to facilitate SDT-induced reactive oxygen species production and enhance SDT efficacy subsequently. The targeted accumulation of these composite nanosonosensitizers efficiently suppressed the growth of U87 tumor xenograft on nude mice after US-triggered SDT treatment. The high <i>in vivo</i> biocompatibility and easy excretion of these multifunctional nanosonosensitizers from the body have also been evaluated and demonstrated to guarantee their future clinical translation, and their TME-responsive <i>T</i>₁-weighted magnetic resonance imaging capability provides the potential for therapeutic guidance and monitoring during SDT

One-Pot Synthesis of Mesoporous Silica Nanocarriers with Tunable Particle Sizes and Pendent Carboxylic Groups for Cisplatin Delivery

Mesoporous silica nanocarriers with tunable particle sizes and different loadings of pendent carboxylic groups were successfully prepared by a straightforward and reproducible strategy, in which carboxyethylsilanetriol sodium salt was co-condensed with tetraethoxyorthosilicate to introduce the carboxylic groups. The key in this strategy was to separate the synthesis process into two steps of the nuclei formation and particle growth. The uniform particle size and ordered structure of the synthesized nanocarriers were manifested by several techniques such as XRD, TEM, SEM, and BET. DLS measurement illustrated that nanocarriers could be well suspended in aqueous solution. The integration and content tunability of the carboxylic groups within mesoporous silica nanoparticles (MSNs) were verified by FT-IR and ²⁹Si NMR. The inherent carboxylic units on the obtained carboxylic group modified MSNs (MSNs-C) effectively enhanced the capture and tailored the release properties of the anticancer drug of cisplatin. The accumulation of drug in the HeLa cells was greatly enhanced due to the highly efficient platinum uptake efficiency transported by the synthesized nanocarriers. The drug encapsulated in the MSNs-C exhibited a higher antitumor activity than free cisplatin against both MCF-7 and HeLa cells

A Two-Dimensional Biodegradable Niobium Carbide (MXene) for Photothermal Tumor Eradication in NIR‑I and NIR-II Biowindows

Conventionally, ceramics-based materials, fabricated by high-temperature solid-phase reaction and sintering, are preferred as bone scaffolds in hard-tissue engineering because of their tunable biocompatibility and mechanical properties. However, their possible biomedical applications have rarely been considered, especially the cancer phototherapeutic applications in both the first and second near-infrared light (NIR-I and NIR-II) biowindows. In this work, we explore, for the first time as far as we know, a novel kind of 2D niobium carbide (Nb₂C), MXene, with highly efficient in vivo photothermal ablation of mouse tumor xenografts in both NIR-I and NIR-II windows. The 2D Nb₂C nanosheets (NSs) were fabricated by a facile and scalable two-step liquid exfoliation method combining stepwise delamination and intercalation procedures. The ultrathin, lateral-nanosized Nb₂C NSs exhibited extraordinarily high photothermal conversion efficiency (36.4% at NIR-I and 45.65% at NIR-II), as well as high photothermal stability. The Nb₂C NSs intrinsically feature unique enzyme-responsive biodegradability to human myeloperoxidase, low phototoxicity, and high biocompatibility. Especially, these surface-engineered Nb₂C NSs present highly efficient in vivo photothermal ablation and eradication of tumor in both NIR-I and NIR-II biowindows. This work significantly broadens the application prospects of 2D MXenes by rationally designing their compositions and exploring related physiochemical properties, especially on phototherapy of cancer

Two-Dimensional Ultrathin MXene Ceramic Nanosheets for Photothermal Conversion

Ceramic biomaterials have been investigated for several decades, but their potential biomedical applications in cancer therapy have been paid much less attentions, mainly due to their lack of related material functionality for combating the cancer. In this work, we report, for the first time, that MAX ceramic biomaterials exhibit the unique functionality for the photothermal ablation of cancer upon being exfoliated into ultrathin nanosheets within atomic thickness (MXene). As a paradigm, biocompatible Ti₃C₂ nanosheets (MXenes) were successfully synthesized based on a two-step exfoliation strategy of MAX phase Ti₃AlC₂ by the combined HF etching and TPAOH intercalation. Especially, the high photothermal-conversion efficiency and <i>in vitro</i>/<i>in vivo</i> photothermal ablation of tumor of Ti₃C₂ nanosheets (MXenes) were revealed and demonstrated, not only in the intravenous administration of soybean phospholipid modified Ti₃C₂ nanosheets but also in the localized intratumoral implantation of a phase-changeable PLGA/Ti₃C₂ organic–inorganic hybrid. This work promises the great potential of Ti₃C₂ nanosheets (MXenes) as a novel ceramic photothermal agent used for cancer therapy and may arouse much interest in exploring MXene-based ceramic biomaterials to benefit the biomedical applications

Metal–Organic Framework Nanosheet Electrocatalysts for Efficient H₂ Production from Methanol Solution: Methanol-Assisted Water Splitting or Methanol Reforming?

Hydrogen (H₂) is presently one of the most promising clean and renewable energy sources, but the conventional hydrogen production by electrochemical water-splitting, though of great potential and extensively studied, is seriously obstructed especially by the anodic oxygen evolution reaction because of its sluggish kinetics. Herein, we report the efficient hydrogen production from methanol solution using facile-synthesized ultrathin 2D bi-metal–organic framework nanosheets (UMOFNs) as a precious metal-free anodic catalyst. The prepared UMOFNs showed a much lowered anodic potential of 1.365 (V vs reversible hydrogen electrode) at 10 mA cm^–2, which was markedly 232 mV lower than that in conventional water splitting, and moreover, the average turnover frequency reached 19.62 s^–1. Benefiting from nearly 100% Faraday efficiency of H₂ production on the counter graphite carbon electrodes without additional electrocatalysts, high-purity hydrogen was produced with enhanced efficiency. More importantly, the anodic electro-reaction mechanism has been evidenced experimentally: the electrocatalytic hydrogen production from the methanol solution is a methanol-assisted water splitting, rather than a methanol-reforming process as claimed in a number of literature studies, in which methanol is oxidized as a sacrificing agent in place of water oxidization in pure water

Facile and Rapid Growth of Nanostructured Ln-BTC Metal–Organic Framework Films by Electrophoretic Deposition for Explosives sensing in Gas and Cr ³⁺ Detection in Solution

Until now, it has been a challenge to prepare lanthanide metal–organic framework films on traditional substrates, like zinc plate, indium oxide (ITO), and fluorine-doped tin oxide (FTO) glasses in a rapid and facile method. In this paper, continuous and dense Ln-BTC MOFs films on unmodified low-cost substrates have been rapidly and easily fabricated though the newly developed electrophoretic deposition (EPD) method in 5 min. Moreover, the as-prepared luminescent films were successfully used for the detection of nitrobenzene (NB), trinitrotoluene (TNT) in gas phases, as well as NB, Cr³⁺ ions for detection in solution

Heteroatomic Se_<i>n</i>S_8–<i>n</i> Molecules Confined in Nitrogen-Doped Mesoporous Carbons as Reversible Cathode Materials for High-Performance Lithium Batteries

A reversible cathode material in an ether-based electrolyte for high-energy lithium batteries was successfully fabricated by homogeneously confining heteroatomic Se_<i>n</i>S_8–<i>n</i> molecules into nitrogen-doped mesoporous carbons (NMCs) <i>via</i> a facile melt–impregnation route. The resultant Se_<i>n</i>S_8–<i>n</i>/NMC composites exhibit highly reversible electrochemical behavior, where selenium sulfides are recovered through the reversible conversion of polysulfoselenide intermediates during discharge–charge cycles. The recovery of selenium sulfide molecules endows the Se_<i>n</i>S_8–<i>n</i>/NMC cathodes with the rational integration of S and Se cathodes. Density functional theory calculations further reveal that heteroatomic selenium sulfide molecules with higher polarizability could bind more strongly with NMCs than homoatomic sulfur molecules, which provides more efficient suppression of the shuttling phenomenon. Therefore, with further assistance of mesopore confinement of the nitrogen-doped carbons, the Se₂S₆/NMC composite with an optimal Se/S mole ratio of 2/6 presents excellent cycle stability with a high initial Coulombic efficiency of 96.5% and a high reversible capacity of 883 mAh g^–1 after 100 cycles and 780 mAh g^–1 after 200 cycles at 250 mA g^–1. These encouraging results suggest that the heteroatomization of chalcogen (such as S, Se, or Te) molecules in mesostructured carbon hosts is a promising strategy in enhancing the electrochemical performances of chalcogen/carbon-based cathodes for Li batteries

Manganese-Loaded Dual-Mesoporous Silica Spheres for Efficient T1- and T2-Weighted Dual Mode Magnetic Resonance Imaging

A novel class of manganese-based dual-mode contrast agents (DMCAs) based on the core–shell structured manganese-loaded dual-mesoporous silica spheres (Mn-DMSSs) for simultaneous T1- and T2-weighted magnetic resonance imaging (MRI) has been successfully reported. The in vitro MR tests demonstrate that the Mn-based DMCAs display an excellent simultaneous T1-weighted and T2-weighted MR imaging effect with a noticeably high T1 relaxivity (<i>r</i>₁) of 10.1 mM^–1s^–1 and a moderately high T2 relaxivity (<i>r</i>₂) of 169.7 mM^–1s^–1. The Mn-based DMCAs exhibit negligible cytotoxicity with >80% cell viability at a concentration of up to 200 μg/mL in human liver carcinoma (HepG2) and mouse macrophage (RAW264.7) cells after 24 h. Confocal laser scanning microscopy (CLSM) results show that the Mn-DMSSs were internalized via endocytosis and located in the cytoplasm but not in the nucleus. The in vivo experiment shows that the signals of rat liver increased by 29% under T1-weighted imaging mode and decreased by 28% under T2-weighted imaging mode in 5 min postinjection of Mn-DMSSs, which reveal that the novel Mn-loaded DMSSs can be used as both positive (T1-weighted) and negative (T2-weighted) MR contrast agents in further biomedical applications