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Mucosal immunization is a powerful weapon against viral infection. In this paper, large pore mesoporous silica nanoparticles (LMSN) with different particle sizes were synthesized for loading influenza split vaccine (SV) to explore the effect of nanoparticle sizes on mucosal immunization and adjuvant efficacy. Interestingly, it was found that among the three particle sizes of nanoparticles, only LMSN-M with around 250 nm could significantly enhance the mucosal immune effect of SV, possessing adjuvant effect. The results indicated that particle size affected the adjuvant effect of LMSN. There was no apparent difference in vaccine loading capacity of LMSN with different particle sizes, but the release of SV depended on the pore length of LMSN. The adjuvant effect of LMSN-M was attributed to its higher cellular uptake performance, intestine absorption and transport efficiency, and the ability to stimulate the maturation of dendritic cells. Simultaneously, compared with LMSN-S and LMSN-L, the more retention of LMSN-M in mesenteric lymph nodes increased the chance of interaction between vaccine and immune system, resulting in the enhanced immunity. This is the first time to study the impact of particle size of LMSN adjuvant on improving mucosal immunity of oral influenza vaccine, and the present work provides a scientific reference for adjuvant design of oral vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered an elegant solution to eradicate tumors due to its minimal invasiveness and low systemic toxicity. Nevertheless, it is still challenging for phototherapy to achieve ideal outcomes and clinical translation due to its inherent drawbacks. Owing to the unique biological functions, diverse gases have attracted growing attention in combining with phototherapy to achieve super-additive therapeutic effects. Specifically, gases such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H 2 S) have been proven to kill tumor cells by inducing mitochondrial damage in synergy with phototherapy. Additionally, several gases not only enhance the thermal damage in PTT and the reactive oxygen species (ROS) production in PDT but also improve the tumor accumulation of photoactive agents. The inflammatory responses triggered by hyperthermia in PTT are also suppressed by the combination of gases. Herein, we comprehensively review the latest studies on gas-synergized phototherapy for cancer therapy, including (1) synergistic mechanisms of combining gases with phototherapy; (2) design of nanoplatforms for gas-synergized phototherapy; (3) multimodal therapy based on gas-synergized phototherapy; (4) imaging-guided gas-synergized phototherapy. Finally, the current challenges and future opportunities of gas-synergized phototherapy for tumor treatment are discussed. STATEMENT OF SIGNIFICANCE: 1. The novelty and significance of the work with respect to the existing literature. (1) Strategies to design nanoplatforms for gas-synergized anti-tumor phototherapy have been summarized for the first time. Meanwhile, the integration of various imaging technologies and therapy modalities which endow these nanoplatforms with advanced theranostic capabilities has been summarized. (2) The mechanisms by which gases synergize with phototherapy to eradicate tumors are innovatively and comprehensively summarized. 2. The scientific impact and interest. This review elaborates current trends in gas-synergized anti-tumor phototherapy, with special emphases on synergistic anti-tumor mechanisms and rational design of therapeutic nanoplatforms to achieve this synergistic therapy. It aims to provide valuable guidance for researchers in this field., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Cyclodextrin (CD)-capped mesoporous silica nanoparticles (MSN) with pH-responsive properties were synthesized, but little research has been carried out to evaluate the impact of critical factors such as the stalk density and the type of CD on the pH-responsive release behavior. Here, the effect of different stalk densities on the pH-responsive release behavior was investigated. Either too low or too high density of the grafted p-anisidine stalk could result in poor cargo release, and the optimum stalk density for MSN was measured by thermal analysis, and found to be approximately 8.7 stalks nm(-2). To achieve effective release control, the CD capes, α-CD and β-CD, were also investigated. Isothermal titration calorimetry (ITC) analysis was employed to determine the formation constants (Kf) of the two CD with p-anisidine at different pH values. The results obtained showed that the complex of β-CD with p-anisidine had excellent pH-responsive behavior as it exhibited the largest changed formation constant (ΔKf) in different pH media. Furthermore, the pH-responsive mechanism between CD and p-anisidine molecules was investigated through ITC and a molecular modeling study. The release of antitumor drug DOX presents a significant prospect toward the development of pH-responsive nanoparticles as a drug delivery vehicle.

A redox-responsive delivery system based on colloidal mesoporous silica (CMS) has been developed, in which 6-mercaptopurine (6-MP) was conjugated to vehicles by cleavable disulfide bonds. The oligosaccharide of hyaluronic acid (oHA) was modified on the surface of CMS by disulfide bonds as a targeting ligand and was able to increase the stability and biocompatibility of CMS under physiological conditions. In vitro release studies indicated that the cumulative release of 6-MP was less than 3% in the absence of glutathione (GSH), and reached nearly 80% within 2 h in the presence of 3 mM GSH. Confocal microscopy and fluorescence-activated cell sorter (FACS) methods were used to evaluate the cellular uptake performance of fluorescein isothiocyanate (FITC) labeled CMS, with and without oHA modification. The CMS-SS-oHA exhibited a higher cellular uptake performance via CD44 receptor-mediated endocytosis in HCT-116 (CD44 receptor-positive) cells than in NIH-3T3 (CD44 receptor-negative) cells. 6-MP loaded CMS-SS-oHA exhibited greater cytotoxicity against HCT-116 cells than NIH-3T3 cells due to the enhanced cell uptake behavior of CMS-SS-oHA. This study provides a novel strategy to covalently link bioactive drug and targeting ligand to the interiors and exteriors of mesoporous silica to construct a stimulus-responsive targeted drug delivery system.

A novel spherical nanosilica matrix (SNM) together with chitosan (CTS) encapsulated SNM (CTS-SNM) was developed in order to investigate the feasibility of using chitosan to regulate drug release rate from porous silica and obtain an oral sustained drug delivery system. To achieve this goal, we synthesized a spherical nanosilica matrix (SNM) and incorporated chitosan chains on the SNM surface. Solvent evaporation method was adopted to load the model drug carvedilol into SNM and CTS-SNM. The physicochemical properties of the drug carriers and drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The structural changes in CTS-SNM in simulated gastrointestinal fluid as well as the relationships between swelling effect of chitosan and in vitro drug release behaviors were investigated. Pharmacokinetic and bioavailability aspects were also discussed. The results showed that the powerful dispersing effect of SNM and the blocking action due to the swelling of chitosan were the two main factors contributing to the sustained drug release behavior. The swelling effect of chitosan in an acidic environment together with the shrinking effect in a relatively alkaline environment allowed regulation of drug release behavior in simulated gastrointestinal fluid. An in vivo study showed that the bioavailability of CAR was improved 182% compared with that of the commercial capsule when SNM was used as the drug carrier. As for CAR-CTS-SNM, the T(max) of CAR was delayed by about 3.4 h and the bioavailability was slightly increased in comparison with the commercial capsule. We believe that SNM and CTS-SNM developed in this study will help increase the use of polymers and inorganic materials in pharmaceutical applications and stimulate the design of oral drug delivery systems for immediate or sustained release of poorly water-soluble drugs.

The purpose of this study was to develop spherical mesocellular foam (MCF) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MCF with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. A model drug, simvastatin (SV), was loaded onto spherical MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The drug release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC demonstrated the successful incorporation of SV into the MCF host. It was found that spherical MCF has a high drug loading efficiency up to 37.5%, and higher than that of fibrous SBA-15 with a pore diameter of 6.5 nm. It is worth noting that fast release rate of SV was obtained from spherical MCF compared with SBA-15 and pure crystalline SV using enzyme-free simulated intestinal fluid (SIF, pH 6.8)., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The purpose of this study was to develop mesoporous silica nanoparticles (MSNs) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MSNs were synthesized using an organic template method in an oil/water phase, and large pore diameter MSNs were functionalized with aminopropyl groups through postsynthesis. MSNs as well as the resulting functionalized MSNs were investigated as matrices for loading and release of the model drug telmisartan (TEL). The effects of different pore sizes and surface chemical groups on TEL uptake and release were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC. The total pore volume and the pore diameter of MSNs were the two main factors limiting the maximum drug load capacity. MSNs allow a very high drug loading of about 60% in weight. The release rate of TEL from MSNs with a pore diameter of 12.9 nm was found to be effectively increased and the release rate of TEL from the functionalized MSNs was effectively controlled compared with that from the unmodified MSNs. We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement and/or sustained release of poorly water-soluble drugs., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Anti-neuroexcitation peptide (ANEP) is a promising candidate for the treatment of neuroexcitation-associated diseases. N-Trimethyl chitosan (TMC) with different degrees of quaternization was synthesized, characterized and evaluated as a brain-targeting delivery vehicle for ANEP. ANEP-loaded TMC nanoparticles were prepared by ionic crosslinking of TMC with tripolyphosphate (TPP). The optimized formulation of nanoparticles consisted of TMC with a degree of quaternization (DQ) of 36.1% and TPP solution with a concentration of 0.6 mg/mL. The mean encapsulation efficiency and loading capacity of the optimum formulation was 80.63% and 185.4 microg/mL, respectively, while the mean particle size, zeta potential, and pH value were 255 nm, 32.0 mV and 6.61, respectively. ANEP was labeled with FITC for in vivo tissue distribution experiments. The results showed that the targetability of ANEP to brain was significantly increased by TMC nanoparticles. Absorptive-mediated transcytosis was believed to be the main pathway for the brain-targeting of FITC-ANEP-TMC/NPs. These findings demonstrate that TMC nanoparticles are potentially useful brain-targeting delivery systems for ANEP., (Copyright 2009 Elsevier B.V. All rights reserved.)

A facile colorimetric Pb2+ assay system has been developed based on the visible color change of gold nanoparticles (GNPs) modified with α2-microglobulin (α2M) protein. The α2M protein is a soluble and high-affinity receptor for Pb2+, which is well studied and regarded as the comparable positive control in Pb-binding protein researches. It was obtained through purifying recombinant protein from the expression of recombinant plasmids in Escherichia coli and was attached on GNPs to form GNPs-α2M sensor nanoparticles for detecting Pb2+, which has never been used for sensing Pb2+ in previous studies. When Pb2+ was introduced into the assay system, GNPs-α2M sensor nanoparticles can be triggered aggregation with the color change from pink to blue. The detection system exhibited good selectivity and sensitivity, which was attributed to the receptor specificity of α2M protein. Using this assay system, it can be distinguished 1.00 μM concentration of Pb2+ or more by naked eyes clearly. Furthermore, the UV-Vis absorbance ratio between 620 and 523 nm exhibited linearity relationship with the concentration of Pb2+ from 0.05 to 3 μM in assay system. In this research, GNPs-α2M sensor nanoparticles have highly specific capability to recognize Pb2+. The assay system constituted by GNPs-α2M sensor nanoparticles displays excellent convenience, selectivity, and sensitivity that provide promising potentials for on-site rapid test of Pb2+. [ABSTRACT FROM AUTHOR]