To date, a variety of delivery systems based on organic or inorganic materials have been investigated. Among them, hydrogels have become one of the most promising field in drug delivery system due to ...their unique properties. Temperature-sensitive hydrogels, which gelation at physiological temperature, gift the delivery system with excellent spatial and temporal control, and have a widely application in drug delivery, tissue engineering, imaging, and wound dressing. This review provides a brief overview on the concept and classification of temperature-sensitive hydrogels, and covers the application of temperature-sensitive gel systems in delivery of biotherapeutic molecules.
Infectious bursal disease (IBD) is an acute, highly contagious, immunosuppressive disease of chickens caused by the virus (IBDV), which critically threatens the development of the global chicken ...industry and causes huge economic losses. As a large country in the poultry industry, the epidemic history of IBDV in China for more than 40 years has been briefly discussed and summarized for the first time in this report. The first classic strain of IBDV appeared in China in the late 1970s. In the late 1980s and early 1990s, the very virulent IBDV (vvIBDV) rapidly swept across the entirety of China, threatening the healthy development of the poultry industry for more than 30 years. Variants of IBDV, after long-term latent circulation with the accumulation of mutations since the early 1990s, suddenly reappeared as novel variant strains (nVarIBDV) in China in the mid-2010s. Currently, there is a coexistence of various IBDV genotypes; the newly emerging nVarIBDV of A2dB1 and persistently circulating vvIBDV of A3B3 are the two predominant epidemic strains endangering the poultry industry. Continuous epidemiological testing and the development of new prevention and control agents are important and require more attention. This report is of great significance to scientific cognition and the comprehensive prevention and control of the IBDV epidemic.
Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity. Currently, gene therapy drugs such as siRNA, shRNA, antisense oligonucleotide, ...CRISPR/Cas9 system, plasmid DNA and miRNA have shown great potential in biomedical applications. To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues, cells and organelles, the development of excellent drug delivery vehicles is of utmost importance. Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression. With the development of nanotechnology, novel nanocarriers are gradually replacing viral vectors, emerging superior performance. This review mainly illuminates the current widely used gene therapy drugs, summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs, and sums up the application of gene therapy to treat genetic diseases. Additionally, the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.
Types of gene therapy drugs, viral and non-viral delivery strategies, and disease treatment status of gene therapy drugs. Display omitted
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Hypoxic tumor microenvironment (TME) is the major contributor to cancer metastasis, resistance to chemotherapy, and recurrence of tumors. So far, no approved treatment has been ...available to overcome tumor hypoxia.
The present study aimed to relieve tumor hypoxia via a nanozyme theranostic nanomaterial as well as providing magnetic resonance imaging (MRI)-guided therapy.
Manganese dioxide (MnO2) was used for its intrinsic enzymatic activity co-loaded with the anti-cancer drug Doxorubicin (Dox) within the recombinant heavy-chain apoferritin cavity to form MnO2-Dox@HFn. Following the synthesis of the nanomaterial, different characterizations were performed as well as its nanozyme-like ability. This nanoplatform recognizes tumor cells through the transferrin receptors 1 (TfR1) which are highly expressed on the surface of most cancer cells. The cellular uptake was confirmed by flow cytometry and fluorescence spectroscopy. In vitro and in vivo studies have been investigated to evaluate the hypoxia regulation, MRI ability and anti-tumor activity of MnO2-Dox@HFn.
Being a TME-responsive nanomaterial, MnO2-Dox@HFn exerted both peroxidase and catalase activity that mainly produce massive oxygen and Mn2+ ions. Respectively, these products relieve the unfavorable tumor hypoxia and also exhibit T1-weighted MRI with a high longitudinal relaxivity of 33.40 mM. s−1. The utility of MnO2-Dox@HFn was broadened with their efficient anti-cancer activity proved both in vitro and in vivo.
MnO2-Dox@HFn successfully overcome tumor hypoxia with double potentials enzymatic ability and diagnostic capacity. This investigation could ignite the future application for cancer theranostic nanozyme therapy.
Infectious bursal disease (IBD) is an acute, highly infectious, and immunosuppressive disease caused by the infectious bursal disease virus (IBDV), which interferes with the immune system, causes ...hypoimmunity and seriously threatens the healthy development of the poultry industry. Adaptive immune response, an important defense line of host resistance to pathogen infection, is the host-specific immune response mainly mediated by T and B lymphocytes. As an important immunosuppressive pathogen in poultry, IBDV infection is closely related to the injury of the adaptive immune system. In this review, we focus on recent advances in adaptive immune response influenced by IBDV infection, especially the damage on immune organs, as well as the effect on humoral immune response and cellular immune response, hoping to provide a theoretical basis for further exploration of the molecular mechanism of immunosuppression induced by IBDV infection and the establishment of novel prevention and control measures for IBD.
Protean mesoporous silica nanoparticles (MSNs) are propitious candidates over decades for nanoscale drug delivery systems due to their unique characteristics, including (but not limited to) ...changeable pore size, mesoporosity, high drug loading capacity, and biodegradability. MSNs have been drawing considerable attention as competent, safer and effective drug delivery vehicles day by day by their towering mechanical, chemical and thermal characteristics. Straightforward and easy steps are involved in the synthesis of MSNs at a relatively cheaper cost. This review reports Stober's synthesis, the first proposed synthesis procedure to prepare micron-sized, spherical MSNs, followed by other modifications later on done by scientists. To ensure the safety and compatibility of MSNs with biological systems, the hemocompatibility evaluation of MSNs using human red blood cells (RBCs) is a widely welcomed exercise. Though our main vision of this overview is to emphasize more on the hemocompatibility of MSNs to RBCs, we also brief about the synthesis and widespread applications of multifaceted MSNs. The strike of different parameters of MSNs plays a crucial role concerning the hemolytic activity of MSNs, which also has been discussed here. The inference is derived by centering some feasible measures that can be adopted to cut down or stop the hemolytic activity of MSNs in the future.
Protean mesoporous silica nanoparticles are propitious candidates over decades for nanoscale drug delivery systems due to their unique characteristics, including changeable pore size, mesoporosity, high drug loading capacity and biodegradability.
The cellular DNA sensor cGMP-AMP synthase (cGAS) detects cytosolic viral DNA via the stimulator of interferon genes (STING) to initiate innate antiviral response. Herpesviruses are known to target ...key immune signaling pathways to persist in an immune-competent host. Marek's disease virus (MDV), a highly pathogenic and oncogenic herpesvirus of chickens, can antagonize host innate immune responses to achieve persistent infection. With a functional screen, we identified five MDV proteins that blocked beta interferon (IFN-β) induction downstream of the cGAS-STING pathway. Specifically, the MDV major oncoprotein Meq impeded the recruitment of TANK-binding kinase 1 and IFN regulatory factor 7 (IRF7) to the STING complex, thereby inhibiting IRF7 activation and IFN-β induction. Meq overexpression markedly reduced antiviral responses stimulated by cytosolic DNA, whereas knockdown of Meq heightened MDV-triggered induction of IFN-β and downstream antiviral genes. Moreover, Meq-deficient MDV induced more IFN-β production than wild-type MDV. Meq-deficient MDV also triggered a more robust CD8+ T cell response than wild-type MDV. As such, the Meq-deficient MDV was highly attenuated in replication and lymphoma induction compared to wild-type MDV. Taken together, these results revealed that MDV evades the cGAS-STING DNA sensing pathway, which underpins the efficient replication and oncogenesis. These findings improve our understanding of the virus-host interaction in MDV-induced lymphoma and may contribute to the development of novel vaccines against MDV infection.
Clinically, indobufen is widely used for the treatment of antiplatelet aggregation and anticoagulation. Prior studies have discovered that abnormal platelet function can be promptly restored to ...normal when the drug is stopped. Herein, through the study of the enzyme reaction kinetics, we demonstrated that the inhibitory effect of indobufen on cyclooxygenase-1 (COX-1) was reversible and non-competitive. Specifically, the cyclooxygenase inhibition experiment showed that the level of 6-keto-PGF1α in the gastric mucosa of the indobufen-treated groups was significantly higher than that of the aspirin group (###p < 0.001), indicating a higher level of PGI2 in and a better physiological state of the gastric mucosa. Moreover, the rat gastric ulcer index and mucosal section experiments further confirmed the relief of gastrointestinal irritation and the adverse reaction rate of the indobufen-treated group compared to those of the aspirin group. Furthermore, indobufen was verified to exert reversible inhibitory activity on the heme group of COX-1 and thus reversibly inhibit COX-1 activity. In general, compared with aspirin, the long-term oral administration of indobufen yields a lower risk of gastrointestinal symptoms, such as ulcers.
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Ferroptosis is a new type of cell death discovered in recent years that distinguishes from apoptosis and necrosis, mainly caused by the imbalance between the production and ...degradation of lipid reactive oxygen species in cells. Although the mechanism of ferroptosis is not yet clear, the phenomenon of ferroptosis has attracted widespread attention from researchers and has become a new hotspot in anti-tumor research. Studies have shown that ferroptosis is involved in the occurrence and development of a variety of diseases such as nervous system diseases, cardiovascular diseases and cancer. And inhibiting or inducing the occurrence of ferroptosis can effectively intervene in related diseases. At the same time, nanotechnology, by virtue of its distinct advantages, has been widely used in the development of nanodrug delivery systems. This review outlines current the advance on the intersection of ferroptosis and biomedical nanotechnology. In this review, the discovery and characteristics of ferroptosis, the mechanism of occurrence and the relationship with disease are summarized. More importantly, we summarized the strategies for inducing ferroptosis based on nanoparticulate drug delivery systems for cancer treatment.
Mesenchymal stem cells (MSC) are particularly effective in promoting cartilage regeneration due to their immunomodulatory, anti-inflammatory and regenerative repair functions of tissues and organs. ...Meanwhile, the intra-articular delivery and synergy with other therapeutic drugs have been the key issues driving their further application. We report a mussel-inspired multifunctional hydrogel system, which could achieve co-delivery and synergism effect of MSC-derived exosomes (Exos) with icariin (ICA). The ICA and Exos co-delivered articular cavity injection system are expected to retain in the joint cavity and promote cartilage regeneration, due to the thermosensitive, self-healing and adhesion properties of the mussel-inspired multifunctional hydrogel. The experimental results proved that Exos enhanced the cellular uptake of ICA by more than 2-fold evenly, and the synergism of Exos and ICA efficiently improve the cell proliferation and migration. After synergic treatment, the content of matrix metalloproteinase 13 in the supernatant and intracellular decreased by 47% and 59%, respectively. In vivo study, ICA-loaded Exos exhibited prolonged retention behavior by multifunctional hydrogel delivery, thus displayed an increased cartilage protection. In the model of osteoarthritis, co-delivery hydrogel system relieved the cartilage recession, ensuring appropriate cartilage thickness.
Schematic of ICA@Exos-loaded hydrogel system for the cartilage repair and regeneration in OA treatment.
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