International Journal of Pharmaceutics-X
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2026
·
IF 7.9
Xiuyun Lin,Hui Li,Jie Liu,Guangfeng Wu,Liuqing Yao,Zhouwei Zhan,Xiufang Yang,Xiu Yang,Shuxian Cai,Na Yao,Fengfang Chen,Wenqiang Yan,Peng Lyu
Neoantigen peptides evade central thymic tolerance due to their absence in normal tissues, making neoantigen vaccines a leading strategy for personalized cancer immunotherapy. Although nanoparticle-based delivery systems are widely used to enhance neoantigen immunogenicity, traditional nanovaccines often incorporate multiple adjuvants and inert carriers, which could hinder efficient antigen delivery and raise biosafety concerns. Herein, we report a carrier-free neoantigen nanovaccine (CpG-2′F/Neo WD ), assembled via fluorination-induced self-assembly for hepatocellular carcinoma (HCC) immunotherapy. This nanovaccine is formed by the co-assembly of fluorinated CpG (CpG-2′F) with the HCC neoantigen peptide (Neo WD ), yielding nanoparticles of approximately 69 nm with a high Neo WD loading efficiency of 67.18 wt%. In vitro studies demonstrate that the nanovaccine potently facilitates dendritic cell uptake and promotes endosomal/lysosomal escape, enhancing antigen cross-presentation efficiency by 2.05-fold compared to the antigen group. In vivo , by efficiently targeting lymph nodes (LNs), the nanovaccine orchestrated both innate and adaptive immune responses against cancer cells, leading to the pronounced expansion of antigen-specific CD8 + T cells and memory T cells. In both prophylactic and therapeutic Hepa1–6 HCC models, this nanovaccine effectively suppressed the progression of poorly immunogenic HCC. Therefore, this study presents a facile, safe and potently immunogenic carrier-free nanovaccine platform for HCC immunotherapy.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Xiaoxuan Fan,Shuxian Zhang,Lingling Yang,Keshuai Liu,Rui Mai,Wangyan Zhao,Yuanyuan Zhang,Bin Guo,Xueqin Ma,Guoning Chen
Developed a signal-amplified fluorescence sensing method for rapid chymotrypsin activity monitoring. • Compared with other methods, this approach exhibits good sensitivity and selectivity. • Enhanced fluorescence sensing was combined with target fishing to construct a chymotrypsin inhibitor screening system. • This integrated platform quantifies chymotrypsin activity and identifies bioactive inhibitors from TCM extracts. Regulation and screening of biomacromolecule (e.g., enzyme) activity is one of the core tasks in disease treatment and drug discovery. Natural products are an important source of enzyme inhibitors, but their complex composition makes it difficult to develop effective candidate drug molecules. As a typical biomacromolecular target, chymotrypsin (CHT) exhibits aberrant activity closely associated with diseases such as wound healing, chronic pancreatitis, and emphysema. Therefore, efficient screening of enzyme inhibitors from natural products holds significant importance for clinical diagnosis, treatment, and drug development. This study establishes an integrated screening platform for enzyme inhibitors by combining a Cu 2+ -casein-mediated fluorescence-enhanced biosensing system with targeted ligand capture technology, enabling highly sensitive screening and precise identification of chymotrypsin inhibitors from natural products. In this platform, Cu 2+ -casein functions as a biomacromolecular substrate while also acting as a peroxidase-mimetic enzyme, significantly enhancing the fluorescence signal amplification effect of o -phenylenediamine oxidation. When chymotrypsin hydrolyzes casein, the structure of casein is disrupted, reducing its copper ion-binding capacity. Which leads to decreased catalytic activity and subsequent changes in fluorescence intensity, allowing quantitative detection of chymotrypsin activity with a detection limit as low as 13.6 ng mL −1 . In the targeted fishing module, immobilized chymotrypsin (CHT@NH 2 -SiO 2 ) is employed as an affinity medium, and combined with HPLC and LC-MS analysis, enables precise identification of active components in complex samples. This integrated strategy mitigates certain limitations of individual techniques, providing a feasible approach for efficient, high-throughput screening of inhibitors targeting biomacromolecules from complex systems. Download: Download high-res image (207KB) Download: Download full-size image
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ACS Nano
·
2026
·
IF 17.3
Wen-Da Wang,Chi-Hui Yang,Wen-Tao Mo,Su-Ran Li,Qi-Chao Yang,Jun Xie,Yun-Hong Zhong,Junjie Zhang,Cong-Fa Huang,Wei-Wei Deng,Xian-Zheng Zhang,Zhi-Jun Sun
The intravenous delivery of oncolytic viruses (OVs) often demonstrates limited therapeutic efficacy due to rapid clearance by peripheral neutralizing antibodies and poor penetration into deeper tumor regions. To overcome these bottlenecks, we report a triple-cascade responsive pneumatic nanomotor (HLNO) designed for systemic delivery of the oncolytic herpes simplex virus (oHSV). The HLNO nanomotor utilizes a hierarchically structured core–shell design featuring an oHSV core encapsulated within a glutathione-responsive liposome layer and hyaluronic acid outer shell while incorporating the pH-sensitive nitric oxide (NO) donor. This system enables immune evasion of oHSV in peripheral circulation while demonstrating programmable activation that specifically responds to tumor microenvironment stimuli. It is noteworthy that the HLNO nanomotor utilizes NO-propelled active motion under acidic conditions to enhance extravasation and tissue deep penetration, followed by hyaluronidase-mediated deshielding and glutathione-triggered oHSV release. Then, the HLNO nanomotor activates the caspase-3/GSDME pathway to induce immunogenic pyroptosis, which enhances antitumor immunity by increasing CD8+ T cell infiltration and M1-like macrophage polarization while driving vascular normalization and alleviating tumor hypoxia. By integrating immune shielding with cascade-responsive release, this platform addresses key limitations of systemic OVs delivery, offering an approach to enhance immunotherapy efficacy in immunologically “cold” tumors.
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-10
·
IF 3.9
Mo Fei,Hong Min,Chen Xiao,Wang Qiye,Dong Chao
The accumulation of regulatory T cells (Tregs) in the tumor microenvironment is a key factor for immunosuppression and immune escape of cancer cells. Genistein is a natural isoflavonoid in soybeans, possessing a wide range of pharmacological bioactivities. However, the immunomodulatory potential of genistein remains largely unexplored. This study investigated the synergistic efficacy of genistein with anti-PD-1 therapy in a mouse model of melanoma. The regulatory role of genistein in Treg differentiation and functional stability was also examined in this study. The antitumor effects of genistein, alone or in combination with anti-PD-1 therapy, were evaluated in the mouse B16-F10 melanoma model. The profiles of intratumoral Tregs and CD8 + cytotoxic T cells were profiled using flow cytometry. The impact of genistein on the suppressive function and differentiation of Tregs was also studied in vitro. RT-qPCR, Western blotting and flow cytometry were conducted to characterize the functional phenotype of Tregs under genistein treatment. Genistein showed a synergistic effect with anti-PD-1 therapy in B16-F10 melanoma models, achieving enhanced immune infiltration and functional reprogramming of the tumor microenvironment. This combinatorial strategy not only reduced intratumoral Tregs but also elevated the CD8 + /Treg ratio. At the mechanistic level, genistein effectively suppressed critical Treg surface markers, which are indispensable for Treg-mediated immunosuppression. Furthermore, it disrupted Treg differentiation by attenuating PI3K/AKT signaling phosphorylation. Our data demonstrated that genistein boosts the antitumor effect of anti-PD-1 therapy by impairing the immunosuppressive function and differentiation of Tregs, indicating that genistein has the potential to enhance the treatment outcome of the immune checkpoint inhibitor.
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MICROCHEMICAL JOURNAL
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2026
·
IF 5.2
Mei Wang,Hui Yuan,Xinmin He,Lingling Yang,Zhigang Yang,Tao Gao,Weibiao Wang,Fen Ma,Weiman Zhang,Gidion Wilson Mening' oo,Yuping Sa,Xiaofei Chen,Guoning Chen,Xueqin Ma
Hyaluronidase (HAase), an enzyme responsible for hyaluronic acid (HA) degradation, compromises the structural integrity of HA by cleaving anti-inflammatory high-molecular-weight HA into pro-inflammatory lower molecular weight forms. Consequently, developing simple and efficient strategies for screening HAase inhibitors is of critical importance. Herein, a novel biosensing-based targeted affinity screening method was established for the identification of HAase inhibitors from complex herbal medicines. In the biosensing system, carbon dots served as fluorescent probes, while HA-functionalized gold nanoparticles acted as quenchers, and the addition of HAase induced a marked fluorescence recovery. Under optimized conditions, HAase exhibited a good linear response over the concentration range of 5.3 to 343.8 U mL −1 . This method enables rapid and efficient detection of HAase inhibitory activity in complex herbal extracts. Subsequently, active components were selectively captured, separated, and identified using immobilized HAase affinity chromatography. Following validation with both negative and positive control drugs, the screening model successfully identified Rhodiola rosea L. among 43 herbal medicines as a potent HAase. Gallic acid (GA) was identified as the active constituent, exhibiting an IC 50 value of 111.7 μM. Results from molecular docking and molecular dynamics simulations demonstrated a strong binding affinity between GA and HAase. Additionally, cellular experiments confirmed the anti-inflammatory activity of GA, as evidenced by its significant inhibition of LPS-induced inflammatory markers IL-4, IL-5, IL-6, and TNF-α. Collectively, the integrated biosensing and affinity-based screening strategy established in this study provides a precise and efficient platform for the discovery of bioactive compounds from complex natural products.
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ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Songchao Duan,Fangfang Sun,Pan Qiao,Zhihui Zhu,Meilin Geng,Xiaobao Gong,Ying Li,Hanchun Yao
In the tumor microenvironment (TME), the extracellular matrix (ECM) produced by cancer-associated fibroblasts (CAFs) forms a dense barrier that prevents nanodrugs from penetrating into deep tumor sites, leading to unsatisfactory therapeutic effects. Recently, it has been found that ECM depletion and using small-sized nanoparticles are effective strategies. Herein, we reported a detachable dual-targeting nanoparticle (HA-DOX@GNPs-Met@HFn) based on reducing ECM for enhancing penetration. When these nanoparticles reached the tumor site, the nanoparticles were divided into two parts in response to matrix metalloproteinase-2 overexpressed in TME, causing a decrease in the nanoparticle size from about 124 to 36 nm. One part was Met@HFn, which was detached from the surface of gelatin nanoparticles (GNPs), which effectively targeted tumor cells and released metformin (Met) under acidic conditions. Then, Met downregulated the expression of the transforming growth factor β by the adenosine monophosphate-activated protein kinase pathway to inhibit the activity of CAFs, thereby suppressing the production of ECM including α-smooth muscle actin and collagen I. The other was the small-sized hyaluronic acid-modified doxorubicin prodrug with autonomous targeting ability, which was gradually released from GNPs and internalized into deeper tumor cells. Intracellular hyaluronidases triggered the release of doxorubicin (DOX), which killed tumor cells by inhibiting DNA synthesis. The combination of size transformation and ECM depletion enhanced the penetration and accumulation of DOX in solid tumors. Therefore, the tumor chemotherapy effect was greatly improved.
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Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 3
·e10475
·
IF 10.684
Chen Zhang,Zhengxiang Cheng,Yuanyuan Zhou,Ziyi Yu,Hongyu Mai,Changhao Xu,Jing Zhang,Jiali Wang
In patients with mild osteoarthritis (OA), two to four monthly injections are required for 6 months due to the degradation of hyaluronic acid (HA) by peroxidative cleavage and hyaluronidase. However, frequent injections may lead to local infection and also cause inconvenience to patients during the COVID-19 pandemic. Herein, we developed a novel HA granular hydrogel (n-HA) with improved degradation resistance. The chemical structure, injectable capability, morphology, rheological properties, biodegradability, and cytocompatibility of the n-HA were investigated. In addition, the effects of the n-HA on the senescence-associated inflammatory responses were studied via flow cytometry, cytochemical staining, Real time quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. Importantly, the treatment outcome of the n-HA with one single injection relative to the commercial HA product with four consecutive injections within one treatment course in an OA mouse model underwent anterior cruciate ligament transection (ACLT) was systematically evaluated. Our developed n-HA exhibited a perfect unification of high crosslink density, good injectability, excellent resistance to enzymatic hydrolysis, satisfactory biocompatibility, and anti-inflammatory responses through a series of in vitro studies. Compared to the commercial HA product with four consecutive injections, a single injection of n-HA contributed to equivalent treatment outcomes in an OA mouse model in terms of histological analysis, radiographic, immunohistological, and molecular analysis results. Furthermore, the amelioration effect of the n-HA on OA development was partially ascribed to the attenuation of chondrocyte senescence, thereby leading to inhibition of TLR-2 expression and then blockade of NF-κB activation. Collectively, the n-HA may be a promising therapeutic alternative to current commercial HA products for OA treatment.
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ANALYST
·
2023
·Vol. 148
·期 6
·1259-1264
·
IF 4.2
Qiannan Li,Yufei Wang,Qianqian Zhu,Haifang Liu,Jianbo Liu,Hong-Min Meng,Zhaohui Li
A novel colorimetric and fluorescent dual-mode sensing system based on molybdophosphoric heteropoly acid (PMA) and fluorescent microspheres (FMs) was established for monitoring the activity of alkaline phosphatase (ALP). In the presence of ALP, L-ascorbic acid-2-phosphate (AAP) could be hydrolyzed catalytically to ascorbic acid (AA), which could reduce PMA to phosphorus molybdenum blue (PMB), accompanied by the generation of colorimetric signals depending on the level of ALP. Meanwhile, the fluorescence of FMs was quenched markedly by the PMB produced due to the inner-filter effect, which constituted the response mechanism for the dual-mode sensing systems of ALP. On this basis, a PMA-FMs based dual-mode sensing system was used for the detection of ALP, which not only possessed remarkable sensitivity, with a limit of detection of 0.27 U L−1 and 0.11 U L−1, but also exhibited good analytical performance in biological samples with satisfactory results. Moreover, a simple and portable test kit for the visual detection of ALP in real serum samples was fabricated utilizing a smartphone with image-recognition and data-processing capabilities as a visual-detection platform.
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Regenerative Biomaterials
·
2023
·
IF 6.7
Pan Zejun,Hou Mingzhuang,Zhang Yijian,Liu Yang,Tian Xin,Hu Xiayu,Ge Xiaoyang,Zhao Zhijian,Liu Tao,Xu Yong,Yang Huilin,Liu Hao,Zhu Xuesong,He Fan
Treating articular cartilage defects in patients remains a challenging task due to the absence of blood vessels within the cartilage tissue. The regenerative potential is further compromised by an imbalance between anabolism and catabolism, induced by elevated levels of reactive oxygen species (ROS). However, the advent of tissue engineering introduces a promising strategy for cartilage regeneration, offering viable solutions such as mechanical support and controlled release of chondrogenic molecules or cytokines. In this study, we developed an antioxidant scaffold by incorporating natural silk fibroin (SF) and kartogenin (KGN)-loaded liposomes (SF-Lipo@KGN). The scaffold demonstrated appropriate pore size, connectivity, and water absorption and the sustained release of KGN was achieved through the encapsulation of liposomes. In vitro experiments revealed that the SF-Lipo@KGN scaffolds exhibited excellent biocompatibility, as evidenced by enhanced cell adhesion, migration, and proliferation of chondrocytes. The SF-Lipo@KGN scaffolds were found to stimulate cartilage matrix synthesis through the activation of the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant signaling pathway. In vivo experiments demonstrated the effective promotion of articular cartilage regeneration by the SF-Lipo@KGN scaffolds, which enhanced extracellular matrix anabolism and restored the intrinsic redox homeostasis. Overall, this study successfully developed biomimetic KGN-loaded scaffolds that restore cartilage redox homeostasis, indicating promising prospects for cartilage tissue engineering.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 17
·9962
·
IF 6.208
Benbo Zhao,Mingda Zhao,Liming Li,Shixiong Sun,Heping Yu,Yuan Cheng,Yuedi Yang,Yujiang Fan,Yong Sun
Natural polymer hydrogels have good mechanical properties and biocompatibility. This study designed hydroxyapatite-enhanced photo-oxidized double-crosslinked hydrogels. Hyaluronic acid (HA) and gelatin (Gel) were modified with methacrylate anhydride. The catechin group was further introduced into the HA chain inspired by the adhesion chemistry of marine mussels. Hence, the double-crosslinked hydrogel (HG) was formed by the photo-crosslinking of double bonds and the oxidative-crosslinking of catechins. Moreover, hydroxyapatite was introduced into HG to form hydroxyapatite-enhanced hydrogels (HGH). The results indicate that, with an increase in crosslinking network density, the stiffness of hydrogels became higher; these hydrogels have more of a compact pore structure, their anti-degradation property is improved, and swelling property is reduced. The introduction of hydroxyapatite greatly improved the mechanical properties of hydrogels, but there is no change in the stability and crosslinking network structure of hydrogels. These inorganic phase-enhanced hydrogels were expected to be applied to tissue engineering scaffolds.Keywords:hyaluronic acid;gelatin;dopamine;double crosslinked;hydroxyapatite-enhanced hydrogel
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Mengru Chen,Jiaqi Lu,Jun Hou,Yanbao Zhao,Lei Sun
Spherical silica carriers have attracted great interest in drug delivery and tumor therapy, but the preparation of non-spherical mesoporous silica carriers with controlled morphology and pores is still a challenge. Here, honeycomb-like mesoporous silica (HMS) nanorods (NRs) were designed and prepared by etching silica nanorods with phosphate buffer solution (PBS). HMS sample possesses an average diameter of 150 nm and length of 450 nm. Their intricate cavities and high specific surface area (724.2 m 2 g -1 ) would provide good prerequisites for drug adsorption and cellular uptake. HMS carriers have an excellent loading capacity of 43% for doxorubicin hydrochloride (DOX). DOX was loaded into the pores of HMS NRs by electrostatic interaction, followed by introducing indocyanine green (ICG) and melting menthol (LM). ICG is used as photosensitizer and LM acts thermal responsive gatekeeper to block the loaded DOX and ICG. Hyaluronic acid (HA) was grafted onto the surface of HMS carriers to achieve targeting effect and responsive drug release under specific environment. The entrapped LM and HA layer could allow the HMS carrier thermal/enzyme/pH responsive release behavior. ICG can produce singlet oxygen and convert light into local heat under laser irradiation. The DOX/ICG-loaded HMS carrier exhibits triple-responsive characters and displays photochemical combination therapy in vitro.
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ACS Applied Nano Materials
·
2022
·
IF 6.14
Sirui Han,Min Fan,Guichan Xu,Wenting Liu,Jingbo Chen,Yudong Lu,Shangyuan Feng,Ruiyun You
As a marker of cellular senescence and abnormal apoptosis, overexpression of β-galactosidase (SA-β-gal) is currently associated with many cancers, Alzheimer’s disease, cataracts, osteoporosis, and other diseases related to cellular senescence. SA-β-gal detection using surface-enhanced Raman scattering (SERS) is increasingly in the spotlight because of its acuteness and efficiency. This study aims to construct a sandwich-structure SERS substrate that can detect SA-β-gal in a sensitive, accurate, and cost-effective way, with a limit of detection of 4.79 × 10–5 U·mL–1. First, gold nanostars (Au NSs) were self-assembled on glass sheets, forming a monolayer gold surface, and the resulting substrate was defined as a gold nanoflake (Au-NF). Then 4-mercaptophenylboronic acid (PMBA) molecules were assembled on it. Lactose molecules served as a bridge between the substrate and SERS tags and were formed by Au NSs modified by PMBA and 4-aminothiophenol (PATP). When SA-β-gal came in contact with the functionalized Au-NF, with the SERS intensity at 1437 cm–1, the characteristic peak of 4,4′-dimercaptoazobenzene (DMAB) formed by PATP through laser irradiation decreased, indicating SA-β-gal activity. This structure allows the use of highly SERS-enhanced Au NSs while creating more hot spots between the SERS tags and substrate and improving the signal intensity without losing reproducibility and has potential in serum testing in the future.
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危险品化学品经营许可证（带存储）