INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Qiyuan Luo,Shiqiang Li,Chenglong Zhang,Yijing Chen,Yun Chen
ALP1 is a structurally defined polysaccharide isolated from Amomum villosum T.L. Wu fruits with an average molecular weight of 26.1 kDa. Previous studies have demonstrated that ALP1 promotes growth performance of piglet by regulating proliferation of intestinal epithelial cells. However, the molecular mechanism remains incompletely understood. In the present study, the absorbability of ALP1 by porcine small intestine epithelial cells and regulating mechanism of ALP1 on cell proliferation were investigated. The results showed that ALP1 resists gastrointestinal degradation and is efficiently absorbed by intestinal epithelial cells via endocytosis. Furthermore, ALP1 facilitates cell cycle progression through upregulating expressions of cdk4 and cyclin e , resulting in an increased proportion of cells in the S and G2/M phases. These findings provide insights into the cellular mechanisms underlying the growth-promoting effects of ALP1 and highlight the potential of dietary polysaccharides as functional agents for enhancing animal growth and gut health.
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高影响因子
Journal of the American Chemical Society
·
2026
·
IF 16.6
Xiaofei Xin,Yifu Lyu,Huanyu Qin,Jinyu Dai,Di Wu,Yu Ding,Qiang Tian,Chao Qin,Na Li,Lifang Yin
The rational design of nonlamellar, multicompartment lipid nanoparticles (LNPs) offers a promising strategy for advancing nucleic acid delivery and immunotherapy. In this study, imidazole-based LNPs (A3-DM/DL-LNPs) with a mesoscopically disordered internal structure resembling the sponge phase were developed, enabling efficient codelivery of mRNA and STAT3-targeting siRNA (siSTAT3). Small-angle scattering analysis revealed a unique quasi-periodic arrangement in A3-DM/DL-LNPs, characterized by broader interdomain spacing and higher membrane heterogeneity compared to benchmark ALC-0315-LNPs, suggesting enhanced endocytosis efficiency and more favorable RNA encapsulation. The “M-shaped” polar headgroup, formed by a piperazine ring flanked by two imidazole moieties, promoted membrane interaction, cellular uptake, and transfection efficiency. In contrast, alternative LNPs with linear polar head structures (A3-SS/SM/SL-LNPs and A4-SS/SM/SL-LNPs) showed inferior delivery performance. Raman spectroscopy revealed that lipid spatial localization correlated with RNA expression in the spleen and lymph nodes, highlighting the importance of LNP structure in immune activation and targeting specific immune organs. Functionally, A3-DM/DL-LNPs restored dendritic cell (DC) antigen presentation, alleviated endoplasmic reticulum (ER) stress, and reversed T cell exhaustion in acute myeloid leukemia (AML), triggering strong immune responses and enhancing natural killer (NK) cell and T cell-mediated antileukemic activity, thereby improving therapeutic outcomes.
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高影响因子
Materials Today Bio
·
2025
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IF 10.2
Yushuang Wei,Wenwen Li,Rong Xu,Cheng Xu,Xiangyang Li,Ning Li,Fengdan Xu,Kai Yang,Bing Yuan
Recent studies have demonstrated that the human antimicrobial peptide LL37 plays a critical role in immune regulation under both normal physiological conditions and during disease progression, as evidenced by its elevated levels observed in various chronic inflammatory diseases. A deeper understanding of its mechanism is essential for elucidating associated physiological and pathological processes, as well as for designing effective immune adjuvants and clinical therapeutics. In this study, we report that LL37 facilitates the assembly of unmethylated CpG dinucleotides (CpG ODNs), a clinically relevant immune adjuvant, into non-crystalline nanoparticles (NPs) with controlled size and zeta potential in a charge ratio-dependent manner. These assembled NPs enter cells via receptor-mediated macropinocytosis, coupled with LL37-mediated membrane penetration, thereby significantly enhancing cellular uptake of CpG compared to CpG alone, which enters cells through clathrin-mediated endocytosis. Consequently, the enhanced internalization of LL37-CpG NPs markedly boosts TNF-α production (>3.5-fold) in macrophages through interactions with lysosomal TLR9. This immunostimulatory mechanism offers an alternative perspective on how LL37 modulates nucleic acid assembly and activates immune cells, providing guidance for the application of peptide-CpG ODN complexes in vaccine adjuvants and immune modulation for disease treatment.
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CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Jinyan Gu,Mouming Zhao,Lijun You,Lianzhu Lin
Rhamnogalacturonan-I type pectin polysaccharide from wolfberry has immunity activity, but its intestinal immunity activity and structure-activity relationship in the small intestine was still unclear. This study comparatively investigated the intestinal immune activity of wolfberry-derived high and low branched Rhamnogalacturonan-I type pectin polysaccharides (H-LBP and L-LBP) and explored the interaction mechanism with mechanical barrier. In the normal mechanical barrier model, both H-LBP and L-LBP could cross mechanical barrier with transport rates of 23.2 % and 25 %, thereby directly enhancing macrophage viability and phagocytic ability after crossing the mechanical barrier. The transport mechanism of H-LBP in mechanical barrier included the clathrin- and caveolin-mediated pathways. In the damaged mechanical barrier model, H-LBP could significantly enhance mechanical barrier integrity, reduce the production of neurotransmitter (NO) and inflammatory cytokine (TNF-α), thereby exerting indirectly intestinal immune activity. Transcriptome analysis showed that the interaction mechanism between H-LBP and damaged mechanical barrier mainly involved signaling pathway regulating cell growth and survival (PI3K-AKT). Western blot experiment and molecular docking simulation confirmed that H-LBP could reduce the expression of p-PI3K, p-AKT and cleaved Caspase3. H-LBP had stronger directly and indirectly intestinal immune activity than L-LBP. These findings were useful for the application of H-LBP in improving intestinal immunity oral formulations.
研究领域:
食品科学
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免疫学
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分子生物学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Huan Tang,Jie Zhou,Tong Yang,Hai-Ning Lyu,Zheng Chu,Ying Zhang,Ang Ma,Junzhe Zhang,Yuqing Meng,Chong Qiu,Sheng-Tao Yang,Jigang Wang,Zipeng Gong
Metal-organic frameworks (MOFs) have garnered substantial interest in the biomedical field due to their unique physicochemical properties, such as high porosity and favorable biocompatibility. Upon exposure to biological environments, biomaterials interact with various proteins that adsorb spontaneously onto their surfaces, leading to the formation and evolution of a protein layer known as the protein corona (PC). However, the composition of the PC on MOFs and its influence on their biological identity remain poorly understood. In this study, we systematically examine protein corona formation on three types of MOF materials (ZIF-8, MIL-53(Fe), and UiO66) in serum, alongside their associated biological effects. Proteomics analysis revealed significant differences in protein corona composition across the three MOFs, particularly in the abundance and types of predominant proteins. Subsequent biological assessments indicated that PC formation mitigated the cytotoxicity, oxidative stress, and immune response of macrophages toward MOFs. Regarding cellular uptake, protein corona formation markedly inhibited the uptake of ZIF-8 and MIL-53(Fe) by macrophages, while enhancing the internalization of UiO66 via clathrin-mediated endocytosis, microtubule-dependent transport, and phagocytosis. Additionally, the PC of these MOFs were enriched with opsonins and dysopsonins that influence phagocytosis. This study is the first to reveal the proteomic composition of PC on these three representative MOFs and to elucidate the role of PC in modulating the biological identities of MOFs in macrophage interactions. These findings offer valuable insights for advancing MOFs-based drug delivery systems in clinical applications and provide new perspectives for exploring the complex physiological behaviors of protein coronas on biomaterials.
研究领域:
生物医学
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材料科学
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蛋白质组学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Xiaochun Wu,Yan Xu,Dandan Zhu,Weiye Zhang,Yanjun Yang,Liang Feng,Bing Yang,Xiaobin Jia
Understanding the absorption of natural polysaccharides is crucial for advancing their development and application. However, their oral absorption mechanisms and potential applications remain unclear. In this study, Astragalus homogeneous polysaccharide (APS3a) was isolated and characterized. Based on the structural analysis, in vitro and in vivo tracking of APS3a was conducted using FITC- and Cy7 amine labeling to investigate its transport and absorption mechanisms. The results indicated that APS3a can traverse the intestinal mucus layer and is mainly absorbed in the jejunum, subsequently distributing gradually to the liver and kidneys. Further investigation of its transport mechanism revealed that APS3a undergoes energy-dependent active transport, utilizing transcellular transport pathways such as caveolin-mediated endocytosis, macropinocytosis, and sodium-glucose cotransporter 1 (SGLT1)-mediated endocytosis. Additionally, APS3a has the capacity to reversibly open tight junction proteins, facilitating transport through the paracellular transport pathway. Moreover, APS3a can function as an excipient, self-assembling with flavonoids from Astragalus Radix to form complexes, thereby enhancing the permeability and absorption of these flavonoids. These findings provide valuable insights into the oral absorption of APS3a and its potential applications, which are significant for the development and application of polysaccharides.
研究领域:
药剂学
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分子药理学
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生物药剂学
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天然产物化学
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药物代谢
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肠道吸收
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纳米药物递送
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Xinchen Zhao,Liyan Qiu
Triple-negative breast cancer (TNBC) is associated with high invasiveness and mortality, with current immunotherapies offering limited clinical benefits. Reduced tumor immunogenicity and dendritic cell (DC) dysfunction are major contributors to tumor immune evasion. Herein, an alkaline phosphatase (ALP)-responsive nanovesicle system (P-DOX/IFN-γ), based on lipid-like polyphosphonitrile (PEBP), was developed for the co-delivery of doxorubicin hydrochloride (DOX) and interferon-γ (IFN-γ), aiming to enhance the therapeutic efficacy against TNBC. The phosphate ester structure facilitates nanovesicle formation and enables multiple interactions with both drugs, thereby efficiently achieving the synchronous encapsulation of DOX within the membrane and IFN-γ in the aqueous cavity. P-DOX/IFN-γ exhibits enhanced tumor targeting and ALP-responsive drug release within the tumor microenvironment. Mechanistically, DOX induces immunogenic cell death in tumor cells, while IFN-γ induces cell cycle arrest and upregulates major histocompatibility complex class I (MHC I) expression, synergistically enhancing tumor immunogenicity and promoting DC activation. As a result, P-DOX/IFN-γ significantly amplifies antitumor immunity and reduces long-term postoperative metastasis in the orthotopic 4T1 tumor model. Overall, this study provides a versatile nanoplatform and a promising immunotherapeutic strategy for TNBC and other poorly immunogenic tumors.
研究领域:
肿瘤学
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药剂学
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免疫学
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高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-15
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IF 15.7
Liu Zhen,Wu Jiacai,Wang Ning,Lin Yongqi,Song Ruiteng,Zhang Min,Li Bin
Despite remarkable progress in designing RNA delivery systems, endosomal escape remains a recognized challenge for efficient RNA delivery. In this study, we develop a robust mRNA delivery platform termed endosomolytic chloroquine-like optimized lipid nanoparticles (ecoLNPs) for versatile mRNA delivery in vitro and in vivo via integrating the signature scaffold extracted from endosomolytic chloroquine into ionizable lipids. RNase-resistant ecoLNPs are capable of delivering a broad variety of mRNA payloads to diverse cell types, even hard-to-transfect 3D cells, with an efficiency of up to 18.9-fold higher than that of commercial transfection reagents. The pH-responsive endosomolytic activity of ecoLNPs can be largely attributed to the proton sponge effect and saposin B-promoted membrane disruption. In vivo, ecoLNPs enable potent local and systemic mRNA delivery and exhibit comparable potency to the clinically approved mRNA vaccine carrier, but strong tropism for lymph nodes following intramuscular injection. Furthermore, ecoLNPs are able to retain in vivo delivery potency for at least one week under non-frozen conditions and induce efficient genome editing in transgenic mice. Overall, the structure-guided integration strategy provides a pathway for de novo design of endosomolytic mRNA delivery systems.
研究领域:
分子生物学
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纳米医学
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药物递送
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Yi Zhang,Hao Guo,Gang Wang,Fang Lan,Shiyong Zhang
The core challenge of H 2 S therapy is to supply H 2 S in a continuous and steady way. By self-polymerizing lipoic acid trisulfide, herein a new H 2 S donor called poly-lipoic acid trisulfide particles (pLATP) is developed with the steady H 2 S supply over 48 h at both cellular and animal levels, the longest time reported so far. Mechanistically, the pLATP high-efficiently enters the cytoplasm via the poly(trisulfides) mediated membrane penetration. In cells, thanks to the polymerized solid sphere structure, the pLATP releases H 2 S by a layer-by-layer decomposed way. Only when the outer layer decomposes, the inner layer can be exposed. After H 2 S release, the pLATP degrades to lipoic acid, which is not only a B vitamin, but also enhances the expression of 3-mercaptopyruvate sulfurtransferase, a H 2 S synthesizing enzyme promoting the production of endogenous H 2 S. The dual pathways of exogenous supplementation and endogenous recovery warrant the continuous and steady supply of H 2 S at the lesion site. As a proof of concept, the pLATP normalized cardiac function in rats with myocardial ischemia-reperfusion injury.
研究领域:
药理学
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生物化学
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纳米医学
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心脏病学
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高分子化学
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高影响因子
VETERINARY RESEARCH
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2018
·Vol. 49
·期 1
·1-9
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IF 2.903
Hu Gaowei,Zheng Wenlv,Li Ao,Mu Yaru,Shi Mingyu,Li Tuofan,Zou Haitao,Shao Hongxia,Qin Aijian,Ye Jianqiang
Cell-penetrating peptide (CPP) is a promising cargo for delivering bioactive molecules. In this study, the N terminus of VP1 from chicken anemia virus, designated as CVP1, was found to carry enriched arginine residues with α-helix. By confocal imaging, flow cytometry and MTT assay, we identified CVP1 as a novel, safe and efficient CPP. CVP1-FITC peptide could entry different types of cells tested with dose dependence, but without cytotoxic effects. Compared with TAT-FITC peptide, the CVP1-FITC peptide showed much higher cell-penetrating activity. Moreover, CVP1 could successfully deliver β-glycosidase, poly (I:C) and plasmid into HCT116 cells. Inhibitors and temperature sensitivity analysis further indicated that the cell-penetrating activity of CVP1 was based on ATP-dependent and caveolae-mediated endocytosis. All these data demonstrate that CVP1 has efficient cell-penetrating activity and great potential for developing a novel delivery vector.
研究领域:
分子生物学
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药学
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细胞生物学
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高影响因子
ADVANCED MATERIALS
·
2021
·Vol. 33
·期 34
·2101707
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IF 30.849
Min Li,Sanpeng Li,Yixuan Huang,Haixia Chen,Songya Zhang,Zhicheng Zhang,Weigang Wu,Xiaobin Zeng,Boping Zhou,Bin Li
The transfer of foreign synthetic messenger RNA (mRNA) into cells is essential for mRNA-based protein-replacement therapies. Prophylactic mRNA COVID-19 vaccines commonly utilize nanotechnology to deliver mRNA encoding SARS-CoV-2 vaccine antigens, thereby triggering the body's immune response and preventing infections. In this study, a new combinatorial library of symmetric lipid-like compounds is constructed, and among which a lead compound is selected to prepare lipid-like nanoassemblies (LLNs) for intracellular delivery of mRNA. After multiround optimization, the mRNA formulated into core–shell-structured LLNs exhibits more than three orders of magnitude higher resistance to serum than the unprotected mRNA, and leads to sustained and high-level protein expression in mammalian cells. A single intravenous injection of LLNs into mice achieves over 95% mRNA translation in the spleen, without causing significant hematological and histological changes. Delivery of in-vitro-transcribed mRNA that encodes high-affinity truncated ACE2 variants (tACE2v mRNA) through LLNs induces elevated expression and secretion of tACE2v decoys, which is able to effectively block the binding of the receptor-binding domain of the SARS-CoV-2 to the human ACE2 receptor. The robust neutralization activity in vitro suggests that intracellular delivery of mRNA encoding ACE2 receptor mimics via LLNs may represent a potential intervention strategy for COVID-19.
研究领域:
纳米技术
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分子生物学
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药学
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病毒学
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治疗学
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高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2020
·Vol. 104
·期 24
·10503-10513
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IF 3.53
Hu Gaowei,Miao Yingjie,Luo Xi,Chu Wenhui,Fu Yongqian
Abstract Cell membranes are a great obstacle for entrance of gene therapeutic agents. Cell-penetrating peptides (CPPs) have been proven as a promising gene delivery tool. However, the early TAT peptide derived from the HIV transcription activator protein has been proven that the sequence contains Furin protease cleaved motifs which limited the TAT application in delivery of exogenous active molecules. In the present study, through the bioinformatics and experimental approach, we have identified a novel CPP derived from the N terminus of VP1 protein of chicken anemia virus (CAV), designated as CVP1-N2, which is rich in arginine residues and contains α-helical structure. Then, the ability of CVP1-N2 cell penetrating was detected using confocal imaging and flow cytometry. FITC-labeled CVP1-N2 peptide could rapidly internalize into different types of live cells with dose dependence and without cytotoxic effects by MTT assay. Surprisingly, CVP1-N2 with a pattern of nuclear sub-location has shown the higher uptake efficiency than TAT. At 10, 1, and 0.1 μM, the mean relative internalization of CVP1-N2 was respectively 1.08-, 12-, and 75-fold higher than that of CVP1, as well as 1.6-, 56-, and 75-fold higher than that of TAT. Moreover, using endocytic inhibitors along with low-temperature stress validated that the CVP1-N2 internalization route is direct translocation pathway. Finally, the capacity of CVP1-N2 for delivery of gene into cells was determined, where it was able to carry red fluorescent protein (RFP) and apoptin genes into cells respectively and induce the apoptosis. All these data indicate that CVP1-N2 could be used as a novel gene delivery vehicle for gene therapy in the future. Key points • 1CVP1-N2 was identified as a novel more efficient cell-penetrating peptide.
• 2. CVP1-N2 localized to the nucleus through the direct transduction pathway.
• 3. CVP1-N2 was able to deliver the apoptin gene into HCT116 cells and induce apoptosis.
研究领域:
分子生物学
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基因治疗
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病毒学
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生物技术
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高影响因子
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