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Drug delivery based on abnormal features of the tumor microenvironment (TME) has attracted considerable interest worldwide. In this study, we proposed an applicable strategy to increase the reactive oxygen species (ROS) and inhibit glutathione (GSH), in an effort to amplify oxidative damage in prostate cancer cells. Specifically, we developed dual-responsive supramolecular self-assembled nanoparticles (NPs) based on polymerized methacrylic acid (MA) and polymerized poly(ethylene glycol) dimethyl acrylate-modified β-cyclodextrin (CD) with ferrocene (Fc)-connected (S) (+)-camptothecin (CPT) (designated as MA-CD/Fc-CPT NPs). The as-prepared negatively charged supramolecular NPs can be taken up by tumor cells successfully owing to their reversible negative-to-positive charge transition capacity at acidic pH. The supramolecular NPs increased ROS generation and decreased GSH to amplify oxidative stress and improve the therapeutic effect of chemotherapy. As expected, MA-CD/Fc-CPT NPs displayed good drug delivery capabilities to tumor cells or tissues. MA-CD/Fc-CPT NPs also inhibited cancer cell proliferation in both the cells and tissues. This result was partially due to increased ROS generation and decreased GSH, which contributed to more pronounced oxidative stress. The as-prepared supramolecular NPs displayed great biosafety to normal tissues. According to our results, negatively charged supramolecular MA-CD/Fc-CPT NPs are well-suited for drug delivery and improved cancer treatment in TMEs.

Natural killer (NK) cells exert cytotoxic effects against infected or stressed cells, such as tumor cells, without the limitation of major histocompatibility complex (MHC) I. NK cells secrete perforins to form tunnels to mediate the entry of granzyme into target cells. This strategy, selected by natural evolution, provides a feasible method for the delivery of antitumor drugs against intracellular targets, and avoids drug-resistant mechanisms in tumor cells, such as the pumping out of drugs mediated by multidrug resistance. We constructed pH-labile artificial NK cells (ANKC) based on nature to mediate high levels of drugs in tumor cells to overcome tumor drug resistance. Mesoporous silicon nanoparticles (MSNs) modified with benzaldehyde were designed to function as scaffolds for ANKC. Doxorubicin (Dox), a model antitumor drug, was loaded into the pores of MSNs. Melittin, a pore-forming peptide, was utilized as the gate for mesopores with an acid-labile Schiff base linkage. pH-labile ANKC released melittin and Dox in slightly acidic tumor microenvironments. Melittin, like perforin, assembled tunnels on the plasma membrane or endosome, ensuring the intracellular transportation of Dox. Dox, similar to granzyme, induced the apoptosis of tumor cells. The combinational treatment partially eased the drug resistance mechanism, such as pumping out of drugs, by continuous intracellular drug accumulation mediated by melittin pores. The pH-labile ANKC demonstrated significant Dox enrichment in drug-resistant MCF-7/Adr cells and MCF-7/Adr-based xenograft tumors in a mouse model, which eventually contributed to efficient inhibition of the proliferation and growth of MCF-7/Adr tumors. PH-labile ANKC provided a potential strategy to treat drug-resistant tumors.

Chemodynamic therapy (CDT), which consumes endogenous hydrogen peroxide (H

The impact of polymer chain stiffness characterized by the bending modulus (kθ) on the glass transition temperature (Tg) of pure polymer systems, as well as polymer nanocomposites (PNCs), is investigated using molecular dynamics simulations. At small kθ values, the pure polymer system and respective PNCs are in an amorphous state, whereas at large kθ values, both systems are in a semicrystalline state with a glass transition at low temperature. For the pure polymer system, Tg initially increases with kθ and does not change obviously at large kθ. However, the Tg of PNCs shows interesting behaviors with the increasing volume fraction of nanoparticles (fNP) at different kθ values. Tg tends to increase with fNP at small kθ, whereas it becomes suppressed at large kθ.

The balance between degradability and drug release kinetics is a major challenge for the development of drug delivery systems. Here we develop hierarchically structured nanoparticles comprising multiple noncontact silica shells using an amorphous calcium carbonate template. The system could be degraded in a sequential fashion on account of the molecularly engineered multishelled structures. The hydrolysis rate of drug-containing cores is inversely correlated with the nanoparticle concentration due to the shielding effect of the hierarchical nanostructure and could be exploited to regulate the release kinetics. Specifically, multishelled nanospheres show a low drug release rate with high doses that increases steadily as the concentration decreases due to continuous degradation, thus stabilizing the local drug concentration for effective tumor therapy. Moreover, the nanoparticles could be eventually degraded completely, which may reduce their health risks. This kind of hierarchically structured silica-based nanoparticle could serve as a sustainable drug depot and provides a new avenue for tumor treatment.

Liver sequestration, mainly resulting from the phagocytosis of mononuclear phagocyte system (MPS) cells, is a long-standing barrier in nanoparticle delivery, which severely decreases the disease-targeting ability, leads to nanotoxicity, and inhibits clinical translation. To avoid long-term liver sequestration, we elaborately designed luminescent gold-silver bimetallic nanoparticles that could be rapidly transformed by the hepatic sinusoidal microenvironment rich in glutathione and oxygen, significantly different from monometallic gold nanoparticles that were rapidly sequestrated by Kupffer cells due to the much slower biotransformation. We found that the rapid sinusoidal biotransformation induced by the synergistic reactions of glutathione and oxygen with the reactive silver atoms could help bimetallic nanoparticles to avoid MPS phagocytosis, promote fast release from the liver, prolong blood circulation, enhance renal clearance, and increase disease targeting. With the fast biotransformation in sinusoids, liver sequestration could be turned into a beneficial storage mechanism for nanomedicines to maximize targeting.

Rhein (RH), a natural anthraquinone compound, is considered an effective treatment candidate for ulcerative colitis (UC), whose multiple biological activities contribute to UC, including anti-inflammation, antioxidation, intestinal barrier repair, and microflora regulation. However, the application of RH is severely limited by its low water solubility, low bioavailability, and poor colonic targeting. Although some nanoparticles have been developed for the oral delivery of RH, most of them mainly highlighted only one effect of some drug delivery strategies but the above multiple biological activities. Therefore, a multiple polysaccharide-based nanodelivery system, comprising chitosan (CS) and fucoidan (FU), with pH/reactive oxygen species (ROS) sensitivity and mucosal adhesion, was developed and first used to load RH as a comprehensive treatment for UC. Briefly, RH-F/C-NPs were prepared using the polyelectrolyte self-assembly method; the average size of RH-F/C-NPs was 233.1 ± 5.7 nm, and the encapsulation rate of RH was 93.67 ± 1.60%. And it could maintain gastric stability and release RH in the colon with the designed pH/ROS sensitivity contributed by the polysaccharide-based structures. Cellular uptake experiments showed that both NCM 460 cells and RAW 264.7 cells had a good uptake of RH-F/C-NPs. Importantly, the effects of RH were highlighted in

Metastasis, as one of major challenges in the cancer treatment, is responsible for the high mortality of breast cancer. It has been reported that breast cancer cell invasion and metastasis are related to aquaporin 3 (AQP3), which is the transmembrane transport channel for H

Cancer immunotherapies such as tumor vaccines, chimeric antigen receptor T cells and immune checkpoint blockades, have attracted tremendous attention. Among them, tumor vaccines prime immune response by delivering antigens and adjuvants to the antigen presenting cells (APCs), thus enhancing antitumor immunotherapy. Despite tumor vaccines have made considerable achievements in tumor immunotherapy, it remains challenging to efficiently deliver tumor vaccines to activate the dendritic cells (DCs) in lymph nodes (LNs). Rational design of nanovaccines on the basis of biomedical nanotechnology has emerged as one of the most promising strategies for boosting the outcomes of cancer immunotherapy. In recent years, great efforts have been made in exploiting various nanocarrier-based LNs-targeting tumor nanovaccines. In view of the rapid advances in this field, we here aim to summarize the latest progression in LNs-targeting nanovaccines for cancer immunotherapy, with special attention to various nano-vehicles developed for LNs-targeting delivery of tumor vaccines, including lipid-based nanoparticles, polymeric nanocarriers, inorganic nanocarriers and biomimetic nanosystems. Moreover, the recent trends in nanovaccines-based combination cancer immunotherapy are provided. Finally, the rationality, advantages and challenges of LNs-targeting nanovaccines for clinical translation and application are spotlighted.

The chemotherapy efficacy of nanodrugs is restricted by poor tumor targeting and uptake. Here, an engineered biohybrid living material (designated as EcN@HPB) is constructed by integrating paclitaxel and BAY-876 bound human serum albumin nanodrugs (HPB) with

Reactive oxygen species (ROS) are important signal molecules and imbalanced ROS level could lead to cell death. Elevated ROS levels in tumor tissues offer an opportunity to design ROS-responsive drug delivery systems (DDSs) or ROS-based cancer therapies such as chemodynamic therapy. However, their anticancer efficacies are hampered by the ROS-consuming nature of these DDSs as well as the high concentration of reductive agents like glutathione (GSH). Here we developed a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde (CA)-based ROS-replenishing organic ligand (TCA). TCA can ROS-responsively release CA to supplement intracellular ROS and deplete GSH by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fesup3+/sup-enabled GSH depletion facilitated efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies revealed that ROS-replenishing PCFD exhibited much better anticancer effect than ROS-consuming control nanoparticle PAFD. The ingenious ROS-replenishing strategy could be expanded to construct versatile ROS-responsive DDSs and ROS-based nanomedicines with potentiated anticancer activity. STATEMENT OF SIGNIFICANCE: We develop a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde-based reactive oxygen species (ROS)-replenishing organic ligand. This functional ligand can ROS-responsively release cinnamaldehyde to supplement intracellular Hsub2/subOsub2/suband deplete glutathione (GSH) by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fesup3+/sup-enabled GSH depletion facilitates efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies reveal that ROS-replenishing PCFD exhibit much better anticancer effect than ROS consuming counterpart. This study provides a facile and straightforward strategy to design ROS amplifying nanoplatforms for cancer treatment.

Despite the extensive explorations of nanoscale metal-organic frameworks (nanoMOFs) in drug delivery, the intrinsic bioactivity of nanoMOFs, such as anticancer activity, is severely underestimated owing to the overlooked integration of the hierarchical components including nanosized MOFs and molecular-level organic ligands and metal-organic complexes. Herein, we propose a de novo design of multifunctional bioactive nanoMOFs ranging from molecular to nanoscale level, and demonstrate this proof-of-concept by a copper-olsalazine (Olsa, a clinically approved drug for inflammatory bowel disease, here as a bioactive linker and DNA hypomethylating agent) nanoMOF displaying a multifaceted anticancer mechanism: (1) Cu-Olsa nanoMOF-mediated redox dyshomeostasis for enhanced catalytic tumor therapy, (2) targeting downregulation of cyclooxygenase-2 by the organic complex of Cu

Chimeric receptor T cells (CAR-T) can effectively cure leukemia; however, there are two limitations: a complicated preparation process ex vivo and cytokine release syndrome (CRS). In this study, we constructed a lipid nanoparticle system modified by CD3 antibody on the surface, loading with the plasmid containing the combination gene of interleukin 6 short hairpin RNA (IL-6 shRNA) and CD19-CAR (AntiCD3-LNP/CAR19 + shIL6). The system targeted T cells by the mediation of CD3 antibody and stably transfected T cells to transform them into CAR-T cells with IL-6 knockdown, thus killing CD19-highly expressed leukemia tumor cells and reducing CRS caused by IL-6. In vivo experiments showed that AntiCD3-LNP/CAR19 + shIL6 could stably transfect T cells and produce CAR-T within 90 days to kill the tumor. This significantly prolonged the survival time of leukemia model mice and demonstrated the prepared LNP exhibited the same anti-tumor effect as the traditional CAR-T cells prepared ex vivo. In this study, CAR-T cells were directly produced in vivo after intravenous injection of the lipid nanoparticles, without the need of using the current complex process ex vivo. Additionally, IL-6 expression was silenced, which would be helpful to reduce the CRS and improve the safety of CAR-T therapy. This method improves the convenience of using CAR-T technology and is helpful in further promoting the clinical application of CAR-T.

Growing evidence demonstrates that the bioaccumulation of polystyrene nanoplastics (PS-NPs) in the gastrointestinal tract has negative effects on health. Until now, little information has been available regarding the potential hazards of PS-NPs to intestinal epithelial barriers. In this study, we employed cellular and animal models to investigate the adverse effects of PS-NPs on intestinal epithelium and the underlying mechanism. We found that PS-NPs affected the growth and survival of intestinal epithelial cells in a time- and concentration-dependent manner. PS-NPs accumulated in the cytoplasm, resulting in an impaired autophagic flux and inducing an autophagic response. This response was also confirmed in vivo. Our results provide new insights into the internalization of PS-NPs and the resultant autophagy response in intestinal epithelial cells.

Anticancer peptides are promising drug candidates for cancer treatment, but the short circulation time and low delivery efficiency limit their clinical applications. Herein, we designed several lasso-like self-assembling anticancer peptides (LASAPs) integrated with multiple functions by a computer-aided approach. Among these LASAPs, LASAP1 (CRGDKGPDCGKAFRRFLGALFKALSHLL, 1-9 disulfide bond) was determined to be superior to the others because it can self-assemble into homogeneous nanoparticles and exhibits improved stability in serum. Thus, LASAP1 was chosen for proving the design idea. LASAP1 can self-assemble into nanoparticles displaying iRGD on the surface because of its amphiphilic structure and accumulate to the tumor site after injection because of the EPR effect and iRGD targeting to αVβ3 integrin. The nanoparticles could disassemble in the acidic microenvironment of the solid tumor, and cleaved by the overexpressed hK2, which was secreted by prostate tumor cells, to release the effector peptide PTP-7b (FLGALFKALSHLL), which was further activated by the acidic pH. Therefore, LASAP1 could target the orthotopic prostate tumor in the model mice after intraperitoneal injection and specifically inhibit tumor growth, with low systematic toxicity. Combining the multiple targeting functions, LASAP1 represents a promising design of self-delivery of peptide drugs for targeted cancer treatments.

Herein, an albumin-enriched nanocomplex was developed for the solubilization and intravascular administration of clopidogrel bisulfate (CLP). In particular, CLP nanoparticles (HS-CLP-NPs) were synthesized via an improved nab-technology method using Solutol HS-15, and bovine serum albumin (BSA) was further enriched on the nanoparticle surface forming a protein corona (BH-CLP-NPs). BH-CLP-NPs displayed an average size of 163.4 ± 10.5 nm, a zeta potential of 1.85 ± 0.03 mV, an encapsulation efficiency of 99.9%, and a drug loading capacity of 32.9%. The cumulative release of CLP from BH-CLP-NPs reached about 60% within 168 h. The pharmacokinetic study on the CLP metabolite indicated that the BSA-enriched nanoparticle showed greater in vivo exposure. Pharmacodynamic studies in the renal ischemia/reperfusion injury rat model further demonstrated the renal protective effect of systemically administered BH-CLP-NPs against acute kidney injury with significantly downregulated blood urea nitrogen and creatinine levels. Overall, the albumin-enriched nanocomplexes offer a neat and efficient strategy for the development of poorly water-soluble drugs to achieve intravascular administration.

Hypoxia-activated prodrugs (HAPs) have drawn increasing attention for improving the antitumor effects while minimizing side effects. However, the heterogeneous distribution of the hypoxic region in tumors severely impedes the curative effect of HAPs. Additionally, most HAPs are not amenable to optical imaging, and it is difficult to precisely trace them in tissues. Herein, we carefully designed and synthesized a multifunctional therapeutic

Breast cancer is still threatening many people’ lives, hence novel targeted therapies are urgently required to improve the poor outcome of breast cancer patients. Herein, our study aimed to explore the potential of nanoparticles (NPs)-loaded with VEGF inhibitors and MED1 siRNA for treatment of the disorder. PEG and MTC conjugates were synthesized by ion gelation, and equipped with VEGF inhibitor (siV) and MED1 (siD) siRNA (MT/PC/siV-D NPs). The size and morphology of the NPs were detected by TEM. Agarose gel experiment was performed to detect drug encapsulation rate and NPs stability. Zeta potential was assessed by immunofluorescence assay and cell uptake was detected by fluorescence analysis. After cancer cells were treated with NPs or PBS, cell proliferation and invasion were evaluated with VEGF and MED1 expression was detected by Western blot and RT-qPCR analyses. Animal model was conducted to confirm the role of NPs in tumor growth. Results showed that, the MT/PC/siV-D NPs exhibited great stability, drug encapsulation and internalization ability. The combined NPs caused decreased proliferation and invasion of tumor cells, inducing M2 macrophages to re-polarize to M1 type with declined expression of VEGF and MED1. Moreover, the NPs remarkably alleviated breast tumor progression. The multifunctional NPs equipped with EGF inhibitors and MED1 siRNA can inhibit tumor progression by targeting TAMs and cancer cells during breast cancer.

Theranostics, which combines both diagnostic and therapeutic capabilities in one dose, has always been an intractable challenge in personalized cancer treatment. Herein, a versatile nanotheranostic platform "nanoflare couple (NC)" has been developed for in situ multiplex cancer-related mRNA imaging and subsequent logic-controlled aggregation of gold nanoparticles, leading to gene therapy and photothermal therapy upon irradiation with infrared light. As a proof of concept, TK1 and survivin mRNAs that are highly expressed in most tumor tissues are selected as endogenous cancer indicators and therapy triggers to design the NC. Mice bearing breast cancer cells MCF-7 are prepared as a model to test its efficacy. The in vitro and in vivo assays validate that the NC show the capability for multiplexed mRNA imaging and high efficiency for logic-controlled combinational therapy of breast cancer.

Nitrate (NO

Microenvironment-responsive drug delivery systems (DDSs) can achieve targeted drug delivery, reduce drug side effects and improve drug efficacies. Among them, pH-responsive DDSs have gained popularity since the pH in the diseased tissues such as cancer, bacterial infection and inflammation differs from a physiological pH of 7.4 and this difference could be harnessed for DDSs to release encapsulated drugs specifically to these diseased tissues. A variety of synthetic approaches have been developed to prepare pH-sensitive DDSs, including introduction of a variety of pH-sensitive chemical bonds or protonated/deprotonated chemical groups. A myriad of nano DDSs have been explored to be pH-responsive, including liposomes, micelles, hydrogels, dendritic macromolecules and organic-inorganic hybrid nanoparticles, and micron level microspheres. The prodrugs from drug-loaded pH-sensitive nano DDSs have been applied in research on anticancer therapy and diagnosis of cancer, inflammation, antibacterial infection, and neurological diseases. We have systematically summarized synthesis strategies of pH-stimulating DDSs, illustrated commonly used and recently developed nanocarriers for these DDSs and covered their potential in different biomedical applications, which may spark new ideas for the development and application of pH-sensitive nano DDSs.

Owing to the rapid and significant progress in advanced materials and life sciences, nanotechnology is increasingly gaining in popularity. Among numerous bio-mimicking carriers, inverse lyotropic liquid crystals are known for their unique properties. These carriers make accommodation of molecules with varied characteristics achievable due to their complicated topologies. Besides, versatile symmetries of inverse LCNPs (lyotropic crystalline nanoparticles) and their aggregating bulk phases allow them to be applied in a wide range of fields including drug delivery, food, cosmetics, material sciences etc. In this review, in-depth summary, discussion and outlook for inverse lyotropic liquid crystals are provided.

Osteoarthritis (OA) is a chronic disease caused by joint inflammation. Its occurrence and development depend on a continuous inflammation environment. The activated M1 macrophages play a critical role in the inflammatory response of OA. Regulating the pro-inflammatory M1 to anti-inflammatory M2 macrophages in the OA articular cavity could be a rational strategy for OA treatment. It has been acknowledged that activated macrophages could proactively capture opsonized nanoparticles in the bloodstream and then accumulate into the reticuloendothelial system (RES) organs. Based on this fact, a trapping strategy is proposed, which transforms a normal nanoparticle into an opsonized attractant to target and regulate macrophage polarization. In this study, the opsonized nanoparticle (IgG/Bb@BRPL) had several key features, including an immunoglobulin IgG (the opsonized layer), an anti-inflammatory agent berberine (Bb), and an oxidative stress-responsive bilirubin grafted polylysine biomaterial (BR-PLL) for drug loading (the inner nanocore). In vitro studies confirmed that IgG/Bb@BRPL prefer to be phagocytosed by M1 macrophage, not M0. And the internalized IgG/Bb@BRPL effectively promoted macrophage polarization toward the M2 phenotype and protected nearby chondrocytes. In vivo studies suggested that IgG/Bb@BRPL significantly enhanced therapeutic outcomes by suppressing inflammation and promoting cartilage repair while not prolonging the retention period compared to non-opsonized counterparts. This proof-of-concept study provided a novel opsonization trapping strategy for OA drug delivery and treatment.

Chunyan Shao,1– 5,* Ziwei Yu,1– 5,* Tongwang Luo,1– 5,* Bin Zhou,1– 5 Quanjiang Song,1– 5 Zhuoyue Li,1– 5 Xiaoqiang Yu,1– 5 Sheng Jiang,1– 5 Yingshan Zhou,1– 5 Wanyu Dong,1– 5 Xingdong Zhou,1– 5 Xiaodu Wang,1– 5 Houhui Song1– 5 1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Hangzhou, Zhejiang, 311300, People’s Republic of China; 2Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, Hangzhou, Zhejiang, 311300, People’s Republic of China; 4China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou, Zhejiang, 311300, People’s Republic of China; 5College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Houhui Song; Xiaodu Wang, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China, Tel +86 15064890670 ; +86 18806537583, Email songhh@zafu.edu.cn; xdwang@zafu.edu.cnIntroduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.Keywords: chitosan-coated selenium nanoparticles, PRRSV, apoptosis, ROS, JNK signaling pathways

A novel electrochemiluminescence (ECL) biosensor for hyaluronidase (HAase) based on the adjustable electrostatic interaction between the surface-charge-controllable nanoparticles and negatively charged electrode has been devised. Hyaluronic acid (HA)-coated amino-modified ruthenium bipyridine-doped silica nanoparticles (Ru@SiO