Search

The liver, a complex and vital organ in the human body, is susceptible to various diseases, including metabolic disorders, acute hepatitis, cirrhosis, and hepatocellular carcinoma. In recent decades, these diseases have significantly contributed to global morbidity and mortality. Currently, liver transplantation remains the most effective treatment for hepatic disorders. Nucleic acid therapeutics offer a selective approach to disease treatment through diverse mechanisms, enabling the regulation of relevant genes and providing a novel therapeutic avenue for hepatic disorders. It is expected that nucleic acid drugs will emerge as the third generation of pharmaceuticals, succeeding small molecule drugs and antibody drugs. Lipid nanoparticles (LNPs) represent a crucial technology in the field of drug delivery and constitute a significant advancement in gene therapies. Nucleic acids encapsulated in LNPs are shielded from the degradation of enzymes and effectively delivered to cells, where they are released and regulate specific genes. This paper provides a comprehensive review of the structure, composition, and applications of LNPs in the treatment of hepatic disorders and offers insights into prospects and challenges in the future development of LNPs.

The toxic effects of organic pollutants and nanoplastics on fish have been extensively studied, but there is limited research available on their combined toxicity to bivalves. This research aimed to investigate the accumulation and ecotoxicological impacts such as antioxidant capacity, histopathology and intestinal microbiota in white hard clam Meretrix lyrata, resulting from 7 days of single and mixture exposure to 3,3',4,4'-tetrachlorobiphenyl (PCB77, 0.1 mg/L) and polystyrene nanoplastics (PS-NPs, 80 nm, 1 mg/L). Our findings revealed that PS-NPs accumulated in various tissues such as the intestine, gill, mantle, foot, and siphon. And when compared to the PCB-PSNPs (PP) co-exposure group, the intestinal fluorescence intensity mediated by plastic particles in the PS-NPs (PS group) was significantly higher. The gill, digestive gland, and intestine were all damaged to varying extent by single exposure to PS-NPs or PCB77, according to histopathological analysis, which was aggravated by PP group. Moreover, the co-exposure induced a higher level of oxidative stress, which reflected by increase of activities of superoxide dismutase, catalase, glutamate oxaloacetate transaminase and glutamic-pyruvic transaminase and malondialdehyde content. In addition, the intestine microbial composition was dramatically altered by the combined exposure, reducing the abundance of probiotics such as Firmicutes, thereby posing a great threat to the health and metabolism of M. lyrata. In conclusion, our findings showed that PS-NPs and PCB77 co-exposure induced a higher toxicity to M. lyrata, including histopathological changes, altered antioxidant capacity and intestinal microbiota disruption. This study provides novel insights into PCB77 and PS-NPs' combined toxicity to marine organisms and its underlying molecular mechanisms of ecotoxicological effects., 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 © 2023. Published by Elsevier B.V.)

Supramolecular self-assembly has gained increasing attention to construct multicomponent drug delivery systems for cancer diagnosis and therapy. Despite that these self-assembled nanosystems present surprising properties beyond that of each subcomponent, the spontaneous nature of co-self-assembly causes significant difficulties in control of the synthesis process and consequently leads to unsatisfactory influences in downstream applications. Hence, we utlized an in situ dynamic covalent reaction based on thiol-disulfide exchange to slowly produce disulfide macrocycles, which subsequently triggered the co-self-assembly of an anticancer drug (doxorubicin, DOX) and a magnetic resonance imaging (MRI) contrast agent of ultrasmall iron oxide nanoparticles (IO NPs). It showed concentration regulation of macrocyclic disulfides, DOX, and IO NPs by a dynamic covalent self-assembly (DCS) strategy, resulting in a stable codelivery nanosystem with high drug loading efficiency of 37.36%. More importantly, disulfide macrocycles in the codelivery system could be reduced and broken by glutathione (GSH) in tumor cells, thus leading to disassembly of nanostructures and intellgent release of drugs. These stimuli-responsive performances have been investigated via morphologies and molecular structures, revealing greatly enhanced dual-modal MRI abilities and smart drug release under the trigger of GSH. Moreover, the codelivery system conjugated with a targeting molecule of cyclic Arg-Gly-Asp (cRGD) exhibited significant biocompatibility, MR imaging, and chemotherapeutic anticancer effect in vitro and in vivo . These results indicated that in situ dynamic covalent chemistry enhanced the control over co-self-assembly and paved the way to develop more potential drug delivery systems.

Glioblastomas (GBMs) are aggressive primary brain tumors with fatal outcome. Traditional chemo-radiotherapy has poor therapeutic effect and significant side effects, due to the drug and radiotherapy (RT) resistance, natural blood-brain barrier, and high-dose RT damage. Even more, tumor-associated monocytes (macrophages and microglia, TAMs) constitute up to 30%-50% of the GBM cellular content, and the tumor microenvironment (TME) in GBM is extremely immunosuppressive. Here, we synthesized nanoparticles (D@MLL) that hitchhike on circulating monocytes to target intracranial GBMs with the assistance of low-dose RT. The chemical construction of D@MLL was DOX·HCl loaded MMP-2 peptide-liposome, which could target monocytes by the surface modified lipoteichoic acid. First, low-dose RT at the tumor site increases monocyte chemotaxis and induces M1 type polarization of TAMs. Subsequently, the intravenous injected D@MLL targets circulating monocytes and hitchhikes with them to the central site of the GBM area. DOX·HCl was then released by the MMP-2 response, inducing immunogenic cell death, releasing calreticulin and high-mobility group box 1. This further contributed to TAMs M1-type polarization, dendritic cell maturation, and T cell activation. This study demonstrates the therapeutic advantages of D@MLL delivered by endogenous monocytes to GBM sites after low-dose RT, and it provides a high-precision treatment for GBMs.

The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants., (© 2022. The Author(s).)

As the use of zinc oxide nanoparticles (ZnO NPs) in everyday products grows, so does concern about health risks. However, no findings on the gastrointestinal toxicity of ZnO NPs have been published. We investigated the possible malignant transformation of ZnO NPs in the mice's colonic tissues using the APC min/+ mouse model with a premalignant lesion in intestinal epithelial cells. Higher doses and long-term oral exposure to ZnO NPs were found to mildly promote colonic inflammation in WT mice, while they moderately or strongly exacerbated the severity of chronic inflammation and tumorigenesis in APC min/+ mice with intestinal adenomatous polyposis. The ZnO NPs-induced inflammation and tumorigenesis in colonic epithelial cells was linked to the activation of CXCR2/NF-κB/STAT3/ERK and AKT pathways. Analysis of the ZnO NPs-exacerbated intestinal adenomatous polyposis in APC min/+ mice revealed that ZnO NPs could activate the APC-driven Wnt/β-catenin signaling pathway, exacerbating intestinal tumorigenesis. In fact, ZnO NPs have been shown to increase intestinal inflammation and tumorigenesis in APC min/+ mice by releasing free Zn 2+ . In WT mice, a low dose of ZnO NPs (26 mg/kg/day) did not cause intestinal inflammation. In conclusion, higher doses and prolonged exposure to ZnO NPs promote the malignant transformation of precancerous epithelial cells., (Copyright © 2021. Published by Elsevier Ltd.)

Near-infrared-II (NIR-II) biowindow is appealing from the perspectives of larger maximum permissible exposure in comparison with the near-infrared-I biowindow, so the NIR-II-responsive drug-delivery nanoplatform is highly desirable. In this work, two-dimensional InSe nanosheets (InSe NSs) are modified with poly(ethylene glycol) and evaluated as an effective NIR-II-responsive cancer treatment nanoplatform. The InSe NSs synthesized by liquid exfoliation exhibit prominent NIR-II-responsive photothermal conversion efficiency (39.5%) and photothermal stability. Moreover, the InSe NSs have a doxorubicin (DOX) loading capacity as high as 93.6%, along with excellent NIR-II-responsive DOX release characteristic. The superior synergistic chemo/photothermal effects have also been demonstrated by the in vitro experiments in killing cancer cells. In combination with good biocompatibility, the InSe NSs have great potential in therapeutic applications.

Pickering emulsions are considered as promising chemical oil repellents in enhanced oil recovery (EOR). In this paper, an amphiphilic block copolymer poly(ethylene glycol)–poly(dopamine methacrylamide) (mPEG–PDMA, abbreviated as mp) containing catechol adhesion groups was synthesized. The surface modification of A200 and SBA-15 nanoparticles was carried out using the strategy of dip-coating with mp solution, and the emulsification properties of the two modified particles and their stability were comparatively investigated. The results showed that both modified particles could achieve excellent emulsification performance. The best emulsification effect was achieved when the concentration of A200-mp and SBA-15-mp particles was 2.5 mg mL−1 and the oil phase volume fraction was 0.5. The emulsions stabilized by SBA-15-mp tended to be invertible when the volume fraction of the oil phase was 0.7 or pH = 2–3 or when NaCl was added, and O/W emulsions could be inverted into W/O types. Interestingly, the emulsions stabilized by A200-mp particles showed good acid resistance, alkali resistance, high salt resistance, multiple oil phase applicability and centrifugal shear stability. In the simulated rock permeation experiments, the emulsions prepared using A200-mp particles could stably permeate in the silica sand column without an obvious chromatographic separation effect, which is promising for application in tertiary oil recovery. [ABSTRACT FROM AUTHOR]

Graphene‐based composite is promising as thermal interface material (TIM) due to its outstanding thermal properties. However, there are some bottlenecks to excellent performance, such as agglomeration of particles and undesirable voids between nanoplatelets. In this work, a composite with three‐dimensional (3D) thermally conductive network has been assembled, which combines three kinds of nanofillers varying geometric dimensions. Thermal conductivity (TC) of composite with graphene nanoplatelets (GNPs) and carbon‐nanotubes (CNTs) at a weight ratio of 3:1 is around 9% higher than that of GNP‐based composite. By the introduction of carbon spheres (CSs), the TC is further increased by 28%. The enhanced thermal property further demonstrated by FLIR infrared camera is attributed to the formation of 3D heat conduction paths by GNPs, CNTs, and CSs, where the GNPs play the role of thermally conductive backbones. The other two components are introduced to attenuate the aggregation and strong thermal anisotropy. Moreover, the TC is confirmed nearly isotropic, which is different from most graphene‐based TIMs because of the in‐plane alignment. Our results indicate that the apparent synergy endows this 3D nanofiller great potential for heat dissipation applications requiring heat removal in two directions. [ABSTRACT FROM AUTHOR]

A Si nanoparticle paste has been studied to form a Si film on a substrate. Rapid thermal annealing (RTA) was conducted in order to recrystallize the Si paste which were prepared by a planetary ball milling grinding n-doped or p-doped Si chips. It was possible to minimize the oxidation during the melting process of Si nanoparticles with this RTA even at 1200 °C in 1 s. Lowering of the melting temperature appears to be due to the size effect and release of surface energy from the Si nanoparticles. RTA was conducted in an infrared furnace with temperatures varying from 1150 to 1300 °C. Si pn homo-junction structure was also fabricated by coating p-type followed by n-type Si pastes on a carbon substrate. Typical rectifying characteristics and slight photo-induced current was observed. [ABSTRACT FROM AUTHOR]

Compartmentalization is an essential feature found in living cells to ensure multiple biological processes occur without being affected by undesired external influences. Here, compartmentalized systems are developed based on the self-assembly of metal-organic framework (MOF) nanoparticles into multifunctional MOF capsules (MOF-Cs). Such MOF-Cs have the capability of controlling molecular transportation and protecting interior microenvironment, thus making tandem reaction along trajectories to desired products. First of all, MOF-Cs present controlled molecular transportation derived from molecular sieving property of MOFs. Second, MOF-Cs can protect the encapsulated cargoes from denaturation and maintain their catalytic activity. Third, MOF-Cs can provide spatial segregation for incompatible species and facilitate communication between these compartments to perform tandem reactions. These compartmentalized structures offer new views in the transportation, microreactor, and biotechnology. [ABSTRACT FROM AUTHOR]