ACS Applied Polymer Materials
·
2025
·
IF 4.7
Jinxuan He,Zhixiang Mou,Lan Chen,Qixian Chen,Xuduan Chen,Lixin Wei
Secondary hyperparathyroidism is driven by pathological overproduction of parathyroid hormone. Surgery is invasive, drug therapy offers only transient control, and both carry substantial side effects. Previous efforts to deliver siRNA to the parathyroid glands achieved only marginal efficacy because the constructs lacked a targeting ligand to overcome the organ’s limited vascular permeability and were rapidly cleared by renal filtration. This study provides a targeted RNA interference therapeutic strategy for treatment of secondary hyperparathyroidism by leveraging the angiogenic characteristics of parathyroid glands via systemic route. Particularly, we manufactured an Arg-Gyl-Asp (RGD)-conjugated siRNA delivery system that exploits the overexpression of integrins and increased vascular permeability in parathyroid glands to achieve preferential siRNA accumulation. The multifunctional cationic copolymers of RGD-poly(ethylene glycol) (PEG)-polylysine-azido [PLys(N3)] and PLys(ss-dibenzocyclooctyne: DBCO) were synthesized and characterized, demonstrating their ability to formulate robust nanocomplexes with small interference RNA [(siRNA): knockdown of parathyroid hormone (PTH)] by virtue of favorable reversible disulfide cross-linking (based on click reaction) post electrostatic complexation. These nanocomplexes exhibited prolonged systemic circulation, preferential accumulation in the angiogenic parathyroid glands, and active intracellular delivery, leading to significant suppression of PTH expression. In a parathyroid hyperplasia mouse model, the siPTH delivery construct from RGD–PEG-PLys(N3)&PLys(ss-DBCO) substantially reduced the serum PTH levels to near-normal values, highlighting the therapeutic potential of our siRNA delivery system. Hence, this RNAi approach outperforms conventional modalities by achieving rapid, potent, and sustained gene knockdown without surgical risk or chronic pharmacologic burden, establishing a paradigm for precision endocrine therapy.
研究领域:
分子生物学
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内分泌学
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纳米医学
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基因治疗
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药理学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Shuai Li,Jianqin Zhang,Hao Wang,Xingyun Zhao,Lin Yang,Lin Chai,Yangyang Liu,Zhangwu Zhao,Bernard Moussian,Abeer El Wakil,Kun Yan Zhu,Zhanghua Zeng,Jianzhen Zhang
RNA interference (RNAi)-based biopesticides, recognized by Science as one of the top ten scientific breakthroughs of 2024, are poised to drive the third revolution in pesticide development. However, the practical applications of RNAi face critical challenges, particularly in overcoming delivery barriers, such as double-stranded RNA (dsRNA) degradation and poor cellular uptake. In this study, we developed a biologically derived melanin nanoparticles (MNP) functionalized with poly- l -lysine (PLL) to deliver dsRNA in Locusta migratoria , a major agricultural pest. The functionalized melanin nanoparticles (MNP-PLL) self-assemble with dsRNA to form MNP-PLL/dsRNA through electrostatic interactions. We evaluated their stability under different environmental conditions, such as in midgut fluid, under various temperature and UV irradiation, demonstrating significantly enhanced resistance to degradation. Bioassays showed substantial improvements in RNAi efficiency and insect mortality. Using fluorescent labeling and pharmacological inhibitors, we further investigated the cellular uptake mechanisms. In contrast to naked dsRNA, chitosan/dsRNA, carbon quantum dots/dsRNA and Spc/dsRNA, MNP-PLL/dsRNA activated three distinct endocytic pathways: clathrin-mediated endocytosis, caveolin-mediated endocytosis, and macropinocytosis, facilitating efficient cellular internalization. Acute toxicity assays confirmed excellent biocompatibility and safety of MNP-PLL to the Western honey bee and zebrafish. This study represents the first application of PLL-functionalized melanin as an efficient nanocarrier to generate MNP-PLL/dsRNA for agricultural pest control, highlighting their strong potential as a next-generation dsRNA delivery platform for sustainable pest management.
研究领域:
农业生物技术
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纳米生物技术
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分子昆虫学
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RNA干扰
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害虫管理
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产品关联
DOI
高影响因子
Journal of Advanced Research
·
2022
·
IF 12.822
Wei Zhang,Mushan Xie,Ioannis Eleftherianos,Amr Mohamed,Yueqing Cao,Baoan Song,Lian-Sheng Zang,Chen Jia,Jing Bian,Nemat O. Keyhani,Yuxian Xia
Introduction Odorant-binding proteins (OBPs) are a class of small molecular weight soluble proteins that exist as expanded gene families in all insects, acting as ligand carriers mediating olfaction and other physiological processes. During fungal infection, a subset of insect OBPs were shown to be differentially expressed. Objectives We tested whether the altered expression of insect OBP s during pathogenic infection plays a role in behavioral or immune interactions between insect hosts and their pathogens. Methods A wide range of techniques including RNAi-directed knockdown, heterologous protein expression, electrophysiological/behavioral analyses, transcriptomics, gut microbiome analyses, coupled with tandem mass spectrometry ion monitoring, were used to characterize the function of a locust OBP in host behavioral and immune responses. Results The entomopathogenic fungus Metarhizium anisopliae produces the volatile compound phenylethyl alcohol (PEA) that causes behavioral avoidance in locusts. This is mediated by the locust odorant binding protein 11 ( LmOBP11 ). Expression of LmOBP11 is induced by M . anisopliae infection and PEA treatment. LmOBP11 participates in insect detection of the fungal-produced PEA and avoidance of PEA-contaminated food, but the upregulation of LmOBP11 upon M . anisopliae infection negatively affects the insect immune responses to ultimately benefit successful mycosis by the pathogen. RNAi knockdown of LmOBP11 increases the production of antimicrobial peptides and enhances locust resistance to M . anisopliae infection, while reducing host antennal electrophysiological responses to PEA and locust avoidance of PEA treated food. Also, transcriptomic and gut microbiome analyses reveal microbiome dysbiosis and changes in host genes involved in behavior and immunity. These results are consistent with the elevated expression of LmOBP11 leading to enhanced volatile detection and suppression of immune responses. Conclusion These findings suggest a crosstalk between olfaction and immunity, indicating manipulation of host OBPs as a novel target exploited by fungal pathogens to alter immune activation and thus promote the successful infection of the host.
研究领域:
昆虫学
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免疫学
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分子生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Qing Liang,Yue Peng,Linyao Zhao,Zhenlin Yang,Xiaowei Chen,Jinfei Li,Zhiyuan Wu,Kun Chen,Bolun Zhou,Yang Liu,Bin Hu,Chunfeng Qu,Moyan Zhang,Shugeng Gao
Neoadjuvant immunotherapy has transformed perioperative approaches for resectable non-small cell (NSCLC) by stimulating anti-tumor immunity preoperatively; however, approximately 50 % of patients fail to show clinical responses. Single-cell RNA sequencing identifies SPP1 + macrophages as a significant obstacle in NSCLC immunotherapy, yet scarce researches have focused on selectively targeting this subset. Herein, we engineer mannose-modified selective organ-targeting lipid nanoparticles (SORT LNPs) that co-load SPP1-siRNA and interferon-γ (IFN-γ) mRNA (siSPP1-mIFNγ@mLNPs) for lung-restricted, mannose receptor-guided delivery to SPP1 + macrophages. Co-encapsulation of siSPP1 and mIFNγ mRNA within mLNPs yields a synergistic effect that surpasses individual encapsulation, as it reverses the M2-like properties of SPP1 + macrophages, diminishes their tumor-promoting functions, and reprograms them towards a tumoricidal phenotype. When combined with the immune checkpoint inhibitors (ICIs) in vivo , siSPP1-mIFNγ@mLNPs significantly boost anti-tumor immune responses in both orthotopic lung cancer and pulmonary metastases. Overall, siSPP1-mIFNγ@mLNPs present innovative perspectives for precise cell-type targeting strategies and position SPP1 + macrophage reprogramming as a clinically actionable strategy to convert ICI non-responders into long-term survivors.
研究领域:
肿瘤学
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免疫治疗
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纳米医学
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分子生物学
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药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Jun Yang,Li-Yuan Sun,Ruiyan Ma,Rui Tang,Juan-Ying Zhao,Qing-Nian Cai
The brown planthopper (BPH), Nilaparvata lugens is a devastating agricultural pest of rice, and they have developed resistance to many pesticides. In this study, we assessed the response of BPH nymphs to nitenpyram, imidacloprid , and etofenprox using contact and dietary bioassays, and investigated the underlying functional diversities of BPH glutathione- S -transferase (GST), carboxylesterase (CarE) and cytochrome P450 monooxygenase (P450) against these insecticides. Both contact and ingestion toxicity of nitenpyram to BPH were significantly higher than either imidacloprid or etofenprox. Under the LC 50 concentration of each insecticide, they triggered a distinct response for GST, CarE, and P450 activities, and each insecticide induced at least one detoxification enzyme activity . These insecticides almost inhibited the expression of all tested GST , CarE , and P450 genes in contact bioassays but induced the transcriptional levels of these genes in dietary bioassays. Silencing of NlGSTD2 expression had the greatest effect on BPH sensitivity to nitenpyram in contact test and imidacloprid in dietary test. The sensitivities of BPH to insecticide increased the most in the contact test was etofenprox after silencing of NlCE , while the dietary test was nitenpyram. Knockdown of NlCYP408A1 resulted in BPH sensitivities to insecticide increasing the most in the contact test was nitenpyram, while the dietary test was imidacloprid. Taken together, these findings reveal that NlGSTD2 , NlCE , and NlCYP408A1 play an indispensable role in the detoxification of the contact and ingestion toxicities of different types of insecticides to BPH, which is of great significance for the development of new strategies for the sucking pest control.
研究领域:
昆虫学
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农业科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Ji Wang,Yanhao Zhang,Chao Liu,Wenhui Zha,Shuo Dong,Hanlei Xing,Xinsong Li
Protein kinase N3 (PKN3), by virtue of its abnormal expression in prostate cells, has been widely used as a target of RNAi (shRNA, siRNA, miRNA) therapy. The major challenges of PKN3 RNAi therapy lie in how to design effective interference sequences and delivery systems. Herein, new PKN3 shRNA sequences (shPKN3-2459 and shPKN3-3357) were designed, and bioreducible, biodegradable, ionizable lipid-based nanoparticles were developed for shPKN3 delivery. First, an ionizable lipid (DDA-SS-DMA) bridged with disulfide bond and ester bonds was synthesized by a three-step reaction and confirmed by MS, 1H NMR, and 13C NMR. The ionizable lipid was mixed with cholesterol, DSPC, PEG-lipid, and shPKN3 by a microfluidic mixer to prepare lipid nanoparticles (LNP–shPKN3) which were characterized by DLS and TEM. Afterward, the pH and glutathione (GSH)-responsiveness of the DDA-SS-DMA based LNP delivery system were investigated by lysosome escape and gel electrophoresis assays. Compared with the commercial transfection reagent Lipo2000, the DDA-SS-DMA based delivery system showed higher transfection efficiency and lower toxicity. Western blot analysis, invasion tests, and migration assays were performed to evaluate the silencing effect of shPKN3 in vitro. In in vivo studies, high tumor suppression (65.8%) and treatment safety were evident in the LNP–shPKN3-2459 treatment group. Taken together, the DDA-SS-DMA based delivery system encapsulating shPKN3-2459 showed significant antitumor efficacy and might be a promising formulation for the treatment of prostate cancer.
研究领域:
药学
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分子生物学
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癌症研究
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Mingtao Tan,Rui Qi,Linyi Meng,Shijie Du,Shanchun Yan,Dun Jiang
Heavy metals are significant environmental pollutants that contribute to widespread contamination. This study demonstrated that Cd transfer through the food chain imparts cross-tolerance to λ-cyhalothrin in Hyphantria cunea larvae. Cd-induced activation of the P450 detoxification system, particularly HcCYP6AE179 and HcCYP9A286, was identified as a critical mechanism for the development of pesticide cross-tolerance in Cd-exposed H. cunea larvae. The dual-luciferase reporter assays, RNAi, and agonist treatment experiment confirmed that HcAhr (Aryl hydrocarbon receptor) upregulated the expression of HcCYP6AE179 and HcCYP9A286. Additionally, H2O2 generation under Cd stress served as a key upstream signal for activating the HcAhr-HcCYP6AE179/HcCYP9A286 detoxification pathway. The nucleic-acid-based pesticides targeting HcAhr, HcCYP6AE179, and HcCYP9A286 exhibited superior stability, biosafety, and gene silencing efficacy. Treatment with these nucleic acid pesticides significantly reduced the tolerance of H. cunea larvae to λ-cyhalothrin in the CK and Cd groups. This work introduces novel approaches for mitigating pesticide cross-tolerance induced by heavy metals.
研究领域:
环境毒理学
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分子昆虫学
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农药科学
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RNA干扰
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生态毒理学
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产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2020
·Vol. 10
·期 2
·285
·
IF 4.082
Ehexige Ehexige,Mingming Bao,Purevbat Bazarjav,Xiang Yu,Hai Xiao,Shuqin Han,Huricha Baigude
Cutaneous melanoma is the most aggressive skin cancer with notorious drug resistance. Inhibition of immune checkpoint molecules is one of the most promising approaches for cancer therapy. Herein, we show that RNAi mediated silencing of STAT3 expression in the tumor tissue robustly inhibit tumor growth in B16F10 mouse model of melanoma. We designed a peptidomimetic-based lipid nanoparticles (LNPs) for the delivery of siRNA in mouse model of melanoma. When systemically administered, the novel formulation (denote DoCh) preferentially delivered siRNA to the tumor tissue. Remarkably, sequential intravenous injections of siRNA against STAT3 induced profound silencing of STAT3 expression in tumor tissue, which resulted in significant downregulation of PD-L1, leading to significant inhibition of tumor growth through inhibition of tumor immune checkpoint. Moreover, DoCh-mediated siRNA delivery did not show noticeable damage to the major organs. Collectively, our data demonstrated that DoCh LNP is a promising tumor-targeted siRNA delivery system.Keywords:peptidomimetic lipid nanoparticle;RNAi;STAT3;PD-L1;cancer immune checkpoints
研究领域:
癌症生物学
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分子生物学
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纳米技术
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免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2024
·
IF 8.1
Lu Wang,Jingjing Miao,Min Ding,Wei Zhang,Luqing Pan
Nonylphenol (NP) contamination in the coastal environment of China poses ecological risks to aquatic organisms. However, the endocrine disruptive impacts of NP on bivalves, particularly on ovarian development, remain poorly understood. In this study, Manila clams Ruditapes philippinarum at the developing stage of gonad were exposed to 1.0 μg/L NP for 21 days. Utilizing RNA interference (RNAi) to suppress ER gene expression, we observed a delay in ovarian development as evidenced by histological observations under both NP and NPRi (NP with ER-RNAi) treatment, with Vtg elevation exclusive to the NP group. Comprehensive analyses encompassing transcriptomics, real-time quantitative PCR, and steroid hormone measurement revealed significant alterations in aldosterone synthesis, estrogen signaling, and thyroid hormone synthesis. These pathways showed similar perturbations in both NP and NPRi groups compared to controls. Notably, the NPRi group exhibited distinct enrichment in PPAR and insulin signaling pathways, may implicating these in ER function suppression. Steroid hormone biosynthesis was notably reduced in both treatments, pointing to a profound impact on hormone synthesis. The contrast between in vivo and in vitro findings suggests that NP's detrimental effects on ovarian development may primarily involve neuroendocrine regulation of steroidogenesis. This investigation highlights the complex dynamics of NP-induced endocrine disruption in bivalves, emphasizing the pivotal role of ER and associated pathways.
研究领域:
环境毒理学
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分子生物学
·
内分泌学
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海洋生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Wenhua Hou,Xiaoxiao Yuan,Linhai Xia,Ni Wang,Zhenyin Zhu,Hongcheng Tang,Jaime C. Piñero,Maohua Chen,Xiong Peng
Sustainable management of insect pests is threatened by insecticide resistance, driving demand for effective, environmentally safe tools. The bird cherry–oat aphid (Rhopalosiphum padi), a major cereal pest, shows resistance to pyrethroids, neonicotinoids, and other insecticide classes. We identified isoferulic acid, a phenolic compound from Prunus padus, as a potent aphicide with lethal and sublethal impacts. Bioassays showed dose-dependent lethality (LC50 = 1.74 mg/L at 48 h), while sublethal exposure shortened adult longevity (17.7 to 10.2 d) and reduced fecundity (81 to 53 nymphs/female). Transcriptomic and enzymatic analyses revealed broad induction of detoxification pathways, with RpLipase consistently upregulated. RNAi-mediated knockdown of RpLipase enhanced susceptibility, lowering the LC50 to 0.85 mg/L and confirming its role in tolerance. Nontarget assays with the predator Harmonia axyridis revealed no acute toxicity. Collectively, isoferulic acid is a promising plant-derived insecticide, and silencing induced detoxification genes enhances its potency, providing a foundation for developing novel resistance-breaking strategies.
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Yinga Wu,Jia Cai,Jingfen Han,Huricha Baigude
Tissue-specific delivery of therapeutic RNAi has great potential for clinical applications. Receptor-mediated endocytosis plays a crucial role in targeted delivery of biotherapeutics including short interfering RNA (siRNA). Previously we reported a novel Curdlan-based nanoparticle for intracellular delivery of siRNA. Here we designed a nanoparticle based on ligand-functionalized Curdlan. Disaccharides were site-specifically conjugated to 6-deoxy-6-amino Curdlan, and the cell line specificity, cellular uptake, cytotoxicity, and siRNA delivery efficiency of the corresponding disaccharide-modified 6-deoxy-6-amino-Curdlan were investigated. Observation by fluorescence microscopy as well as flow cytometry showed that galactose-containing Curdlan derivatives delivered fluorescently labeled short nucleic acid to HepG2 cells expressing ASGPR receptor but not in other cells lacking surface ASGPR protein. Moreover, highly galactose-substituted Curdlan derivatives delivered siRNA specifically to ASGPR-expressing cells and induced RNAi activities, silencing endogenous GAPDH gene expression. Our data demonstrated that galactose-functionalized 6-deoxy-6-amino-Curdlan is a promising carrier for short therapeutic nucleic acids for clinical applications.
研究领域:
生物技术
·
分子生物学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Xiaodan Tan,Wenjia Guo,Zhe Peng,Chao Gu,Pu Xiang,Yujun Tu,Huizhi Fei,Xia Liu,Yi Lu,Miaomiao Li,Hong Wang,Ying Luo,Junqing Yang
Based on the previous studies, this study was carried out to explore the interaction of LncRNA-Malat1/miR-211-5p in cerebral ischemia reperfusion injury (CIRI). Firstly, the expression changes of LncRNA-MALAT1 and miR-211-5p in ischemia patients’ blood were determined, and the binding sites of them were predicted by bioinformatics. Furthermore, middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established in adult male SD rats , and primary neuronal oxygen-glucose deprivation/reoxygen-glucose reoxygenation (OGD/R) was established in vitro. The results showed that LncRNA-MALAT1 was significantly up-regulated and miR-211-5p down-regulated in the peripheral blood of patients with ischemic stroke, and the expression changes were negatively correlated. Bioinformatics prediction results showed that LncRNA-MALAT1 had a binding site with miR-211-5p. We also found that LncRNA-Malat1 was significantly up-regulated while miR-211-5p down-regulated in rat cortex tissue and primary neurons treated with OGD/R. In addition, lentivirus interfered with LV-Malat1-RNAi decreased the expression of LncRNA-Malat1 and promoted the up-regulation of miR-211-5p. Combination of LV-Malat1-RNAi and miR-211-5p inhibitor significantly reversed the protective effect of down-regulation of LncRNA-Malat1. Inhibition of LncRNA-Malat1 expression alleviated the neurological deficit score after MCAO/R, improved histopathological damage, and reduced the size of cerebral infarction . Combined administration of LV-Malat1-RNAi + Antagomir-211-5p reversed these effects above. In short, our data suggest that LncRNA-Malat is involved in the occurrence and development of cerebral ischemia reperfusion injury by acting on miR-211-5p and is then regulating the expression of COX-2.
研究领域:
神经科学
·
分子生物学
·
医学遗传学
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DOI
PubMed
高影响因子
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