CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hang Ruan,Yuwen Zhong,Huining Ding,Zehui He,Jiaqi Li,Meng Long,Zhi Wang,Qing Xia,Teng Guo,Chunyun Zhu,Tao Yang,Nianping Feng,Yongtai Zhang
Licorzinc is a commonly used immunomodulator, but faces poor water solubility, high oral dose, and side effects of zinc accumulation by long-term administration. Herein, a new licorzincform was developed by adsorbing glycyrrhizic acid (GA) into zeolitic imidazolate framework-8 (GA@ZIF-8) with superior solubility and acid-responsive drug release properties. Then, a dual-continuous microneedle patch was developed for simultaneous transdermal delivery of GA@ZIF-8 and monitoring Zn 2+ in local tissues, where dissolving microneedles as a drug delivery unit were fabricated from hyaluronic acid. In contrast, swollen hydrogel microneedles as a diagnostic unit were prepared from double cross-linking of N-acryloyl-glycinamide and α-methylacrylic acid and hybridized with Eu 3+ and terpyridine (TPy). The microneedles for transdermal GA@ZIF-8 delivery were completely dissolved in 2 min, which improved the cyclophosphamide-induced hair follicle recession in mice by reducing CD8 + NKG2D + T cells infiltration, inhibiting Jak receptor activation, and decreasing IL-15 and IFN-γ. Additionally, as a sensor unit, the microneedles rapidly absorbed water swelled when stabbed into the skin, and fluoresced red when exposed to 365 nm light. Zn 2+ in the inter tissue fluid competes with Eu 3+ in the TPy-Eu 3+ complex and coordinates with Tpy, which triggers a change in fluorescence. Notably, the detection Zn 2+ concentration range was 10 –8 M–10 –1 M, and it was not disturbed by metal ions including Na + , K + , Mg 2+ , and Ca 2+ , suggesting that it is competent to be applied as a real-time chemosensor of Zn 2+ . Collectively, this newly designed system with both therapeutic and diagnostic functions provides a new strategy for treating zinc-related diseases.
研究领域:
药学
·
材料科学
·
生物医学工程
·
皮肤科
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2013
·
IF 5.695
Wenjiao Zhou,Xue Gong,Yun Xiang,Ruo Yuan,Yaqin Chai
The employment of DNAzyme probes for visual biodetections has received increasing interest recently due to the simple nature of this type of assay. However, achieving high sensitivity and detecting targets beyond nucleic acids remain two major challenges in DNAzyme-based visual detections. In this work, based on a new quadratic amplification strategy, we developed a sensitive and visual detection method for cytokines by using hairpin aptamer DNAzyme probes. The target cytokine, interferon γ (IFN-γ), associates with the aptamer sequences and unfolds the hairpin structure of the probes, leading to simultaneous recycling of the target IFN-γ (assisted by Bst-polymerase) and the DNA sequences (aided by λ exonuclease) to achieve quadratic amplification. This quadratic amplification results in the generation of numerous peroxidase-mimicking DNAzymes, which cause significantly intensified color change of the probe solution for highly sensitive detection of IFN-γ by the naked eye down to 50 pM. The proposed visual sensing method shows also high selectivity toward the target IFN-γ and can be performed in homogeneous solutions with using completely unmodified, synthetic aptamer DNAzyme probes. These distinct advantages of our developed assay protocol make it a potential platform for detecting various types of biomolecules with careful probe designs.
研究领域:
生物化学
·
分析化学
·
分子生物学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Jianxiang Xu,Yanyan Zhang,Yilu Zheng,Tong Wang,Huan Zhang,Kai Wang,Yu Wang,Gareth R. Williams,Li-Min Zhu
In this work we present a near-infrared (NIR)-operated nanoswitch based on chitosan nanoparticles (EpCAM-CS-co-PNVCL@IR780/IMQ NPs) that induces cascade immunogenic tumor ferroptosis via cytokine storm. The formulation was prepared by loading a photosensitiser (IR780) and an immunotherapeutic drug (imiquimod; IMQ) into temperature- and pH-responsive chitosan-based NPs functionalized with tumor-targeting aptamers. The EpCAM aptamer can chaperone the NPs selectively into cancer cells, and allow them to enter the cell nucleus. In vi tr o and in vi v o assays revelaed that the NPs were able to effectively induce the immunogenic ferroptosis of cancer cells. Under NIR irradiation, EpCAM-CS-co-PNVCL@IR780/IMQ cause cell death in tumors via photothermal therapy. Moreover, IMQ promotes the maturation of dendritic cells (DCs), which then activate cytotoxic T-lymphocytes (CTLs); these T-cells go on to provide immunotherapy of metastatic tumor cells. The metastatic tumor cells can be induced to undergo ferroptosis by the addition of arachidonic acid (AA), which interacts with interferon cytokines (IFN- γ ) released from CTLs.
研究领域:
癌症治疗
·
纳米技术
·
免疫疗法
·
生物医学工程
·
药学科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Lu Chenhe,Li Haimin,Chen Wenjing,Li Hui,Ma Jiayu,Peng Peng,Yan Yan,Dong Weiren,Jin Yulan,Pan Shiyue,Shang Shaobin,Gu Jinyan,Zhou Jiyong
Introduction: Variant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion.Methods: We reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus.Results: An immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells.Conclusion: Collectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.
研究领域:
病毒学
·
免疫学
·
分子生物学
·
疫苗开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ophthalmology
·
2016
·
IF 1.463
Hongyan Zhou,Wensong Zhang,Xunyi Gao,Hongguang Zhang,Ning Kong
Purpose. The study aimed to evaluate the effect of all-trans retinoic acid-loaded nanostructured lipid carriers (ATRA-NLCs) on the zymosan-induced expression of the cytokines IL-4, IL-10, and IFN-γ and the matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) and TLR2 in rabbit corneal fibroblasts (RCFs). Methods. ATRA-NLCs were prepared by emulsification. RCFs were isolated and harvested after four to seven passages in monolayer culture. Cytokine release (IL-4, IL-10, and IFN-γ) induced by zymosan was analyzed by cytokine release assay, reverse transcription, and real-time polymerase chain reaction (RT-PCR) analysis detection. MMP-1, MMP-3, and MMP-13, TIMP-1 and TIMP-2, and TLR2 expression were analyzed by immunoblotting. Results. ATRA-NLCs were resistant to light and physically stable, and the average size of the ATRA-NLCs was 200 nm. ATRA-NLCs increased the zymosan-induced release of IL-4 and IL-10 and decreased the release of IFN-γ by RCFs. ATRA-NLCs decreased the levels of TLR2 and MMPs/TIMPs above. Conclusions. ATRA may be a potent anti-inflammatory agent for the therapy of fungal keratitis (FK).
研究领域:
药理学
·
眼科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yuanyuan Wen,Kaiming Li,Mengnan Ni,Hui Jiang,Haisi Wu,Qinqi Yu,Jinyu Li,Xiaolin Li,Jifu Wei,Wei Wu,Huae Xu
Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2024
·
IF 3.3
Tongyu Zhang,Yawen Tian,Xiao Zhang,Wenfeng Wang,Yingkai He,Chongbo Ge,Futing Jia,Zhannan Wang,Yanlong Jiang
The H9N2 avian influenza virus (AIV) is spreading worldwide. Presence of H9N2 virus tends to increase the chances of infection with other pathogens which can lead to more serious economic losses. In a previous study, a regulated delayed lysis Salmonella vector was used to deliver a DNA vaccine named pYL233 encoding M1 protein, mosaic HA protein and chicken GM-CSF adjuvant. To further increase its efficiency, chitosan as a natural adjuvant was applied in this study. The purified plasmid pYL233 was coated with chitosan to form a DNA containing nanoparticles (named CS233) by ionic gel method and immunized by intranasal boost immunization in birds primed by oral administration with Salmonella strain. The CS233 DNA nanoparticle has a particle size of about 150 nm, with an encapsulation efficiency of 93.2 ± 0.12 % which protected the DNA plasmid from DNase I digestion and could be stable for a period of time at 37°. After intranasal boost immunization, the CS233 immunized chickens elicited higher antibody response, elevated CD4 + T cells and CD8 + T cells activation and increased T-lymphocyte proliferation, as well as increased productions of IL-4 and IFN-γ. After challenge, chickens immunized with CS233 resulted in the lowest levels of pulmonary virus titer and viral shedding as compared to the other challenge groups. The results showed that the combination of intranasal immunization with chitosan-coated DNA vaccine and oral immunization with regulatory delayed lytic Salmonella strain could enhance the immune response and able to provide protection against H9N2 challenge.
研究领域:
免疫学
·
病毒学
·
兽医学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Wenjing Mo,Shujie Liu,Xiaozhi Zhao,Fayun Wei,Yuhang Li,Xinan Sheng,Wenmin Cao,Meng Ding,Wenlong Zhang,Xiaoqing Chen,Longxiyu Meng,Sheng Yao,Wenli Diao,Hui Wei,Hongqian Guo
Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME), represent fundamental barriers in cancer immunotherapy, whereas current nanomedicines rarely exert dual modulatory roles on these cell types simultaneously. Reactive oxygen species (ROS) not only mediates MDSC-induced immunosuppression but also triggers differentiation and polarization of M2-TAMs. Herein, an ROS scavenging nanozyme, Zr-CeO, with enhanced superoxide dismutase- and catalase-like activities for renal tumor growth inhibition is reported. Mechanistically, intracellular ROS scavenging by Zr-CeO significantly attenuates MDSC immunosuppression via dampening the unfolded protein response, hinders M2-TAM polarization through the ERK and STAT3 pathways, but barely affects neoplastic cells and cancer-associated fibroblasts. Furthermore, Zr-CeO enhances the antitumor effect of PD-1 inhibition in murine renal and breast tumor models, accompanied with substantially decreased MDSC recruitment and reprogrammed phenotype of TAMs in the tumor mass. Upon cell isolation, reversed immunosuppressive phenotypes of MDSCs and TAMs are identified. In addition, Zr-CeO alone or combination therapy enhances T lymphocyte infiltration and IFN- γ production within the TME. Collectively, a promising strategy to impair the quantity and function of immunosuppressive myeloid cells and sensitize immunotherapy in both renal and breast cancers is provided.
研究领域:
癌症免疫治疗
·
纳米医学
·
免疫学
·
肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Liping Qian,Lihua Mao,Weixing Mo,Rong Wang,Yunlong Zhang
Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3+CD8+T cells and IFN-γ+CD8+T cells were enhanced, while (CD4+CD25+Foxp3)/CD4+T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN-γ levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.
研究领域:
肿瘤学
·
放射学
·
免疫学
·
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Shang,He Yan,Huang Xin,Shen Yao,Zou Qingshuang,Yang Gun,Fu Li,Liu Quan,Luo Dixian
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract
研究领域:
癌症生物学
·
纳米技术
·
免疫疗法
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Yi Chen,Hongjin Qian,Dandan Peng,Yan Jiang,Qiaolin Liu,Yan Tan,Longbao Feng,Biao Cheng,Guilan Li
Wound infection is a major problem faced during wound healing. Therefore, it is necessary to develop wound dressings with excellent antimicrobial properties. Here, a smart response system of PVA-TPE/HA-AMP/SF/ALG wound dressing was prepared by a combination of chemical cross-linking and freeze-drying methods. We grafted AMP onto HA to endow the wound dressing with bacterial resistance and slow release of AMP. At the same time, the system detects bacterial activity in real time for precise antimicrobial activity (through the use of PVA-TPE) and modulates inflammation to reduce bacterial infection (through the use of AMP). In addition, the PVA-TPE/HA-AMP/SF/ALG wound dressing has a good three-dimensional mesh structure, which promotes cell proliferation, enhances collagen deposition and angiogenesis, and thus effectively promotes rapid healing of infected wounds. Moreover, it can induce the expression of inflammatory factors such as VEGF, TNF-α, IFN-γ, IL-4 and TGF-β1 in infected wounds through the Wnt/CAMK/p-PKC signaling pathway, inhibit inflammatory responses, promote wound healing and reduce scar formation. Therefore, the PVA-TPE/HA-AMP/SF/ALG wound dressing smart response system shows great promise in infected wound healing.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·
IF 3.7
Lida Feng,Guixiao Huang,Qifang Lei,Mingkang Liang,Dashi Deng,Xiaocen Liu,Chenfan Kong,Chenchen Li,Xiyang Tan,Guangzhi Li,Song Wu
Intravesical instillation-based immunotherapy for bladder-preservation of bladder cancer (BCa) treatment has not been explored. In the current study, two irrigated nano-formulations of immunological adjuvant-fluorinated chitosan (FCS) and therapeutic antibody-FCS are developed for synergistic immunotherapy against BCa. In this system, FCS is employed as a transepithelial carrier to assemble with bovine serum albumin (BSA)-flubendazole (FBZ) complex and anti-PD-1 (αPD-1) respectively, to facilitate efficient transepithelial delivery of intravesical FBZ-BSA and αPD-1 though transiently regulating the distribution of tight junction proteins on bladder epithelium. In addition, the FBZ–BSA complex exhibits tumor microenvironment-responsive charge reversal and BSA carrier-broken effects to drive tumor-targeted dissociation and drug release of FBZ–BSA/FCS. Moreover, FBZ not only promotes apoptosis and inhibits glycolysis in cancer cells but also displays adjuvant properties to activate potent immune responses through IL-12/IFN-γ pathway. Interestingly, combined perfusion of FBZ–BSA/FCS and αPD-1/FCS nano-formulations can significantly activate the tumor immune microenvironment, especially CD8 + T cell infiltration and αPD-1 sensitivity, and finally remarkably inhibit tumor growth in the mouse orthotopic BCa model. Thus, this study presents a novel intravesical delivery platform for ICB antibodies and a smart adjuvant system to achieve potent synergy immunotherapy, which is promising for bladder-preserving treatment against BCa.
研究领域:
药学
·
癌症研究
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）