ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Xiaoxue He,Tian Liu,Mingjia Sun,Linsheng Wu,Yinghou Wang,Jingdong Xiao,Jin Sun,Qikun Jiang
Small interfering RNAs (siRNAs) have emerged as promising therapeutics for ulcerative colitis (UC) owing to their potent anti-inflammatory effects and favorable biocompatibility. However, effective oral siRNA delivery remains challenging due to limited inflammatory cell targeting, inefficient endosomal escape, and rapid degradation in the gastrointestinal tract. To overcome these barriers, we developed a nano-in-micro modular microbead system for colon-targeted delivery of siRNA against tumor necrosis factor-α (TNF-α). This platform integrates two key components: (i) a library of ginsenoside-based lipid nanoparticles (LNPs) generated by screening natural sterol analogues, among which ginsenoside Rg3-based LNPs (Rg3@siTNF-α) were identified as optimal carriers, enabling enhanced macrophage targeting via glucose transporter-1–mediated recognition and promoting endosomal escape by attenuating Niemann–Pick C1 (NPC1)–dependent recycling; and (ii) a calcium alginate (CA) shell that encapsulated Rg3@siTNF-α to form microbeads (CA@Rg3@siTNF-α), protecting the LNPs from premature degradation in the upper gastrointestinal tract. Upon colon-specific dissolution, CA@Rg3@siTNF-α released Rg3@siTNF-α, facilitating efficient macrophage uptake, rapid endosomal escape, and lipase-responsive siRNA release. Consequently, the microbeads alleviated UC by suppressing inflammation and oxidative stress, restoring epithelial barrier integrity, and rebalancing the gut microbiota. Collectively, this work presents a spatiotemporally controlled strategy for oral siRNA delivery with multi-mechanistic therapeutic actions.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Li Qiao,Xue-Tian Qian,Yi-Gang Zhang,Xia-Feng Peng,Qi Liu,Shi-Qi Chang,Chang Cui,Feng Zhang,Shu-Kui Wang,Ning-Ping Huang
A novel Eudragit S100-coated and mannose-modified liposome enables colon-specific and macrophage-targeted siRNA delivery. EML/siRNA exhibit excellent stability, biocompatibility, and efficient intracellular delivery siRNA. • The nanocarrier protects TNF-α siRNA from Gastrointestinal (GI) degradation and achieves responsive release in the colon. • Treatment in IBD models significantly downregulates pro-inflammatory cytokines and promotes tissue repair. • The platform provides a targeted and improved therapeutic strategy for precise IBD management. Inflammatory bowel disease (IBD) is a chronic and clinically important intestinal disorder with rapidly rising global incidence and prevalence. While biological therapies targeting tumor necrosis factor-alpha (TNF-α), a key cytokine in IBD pathogenesis, have shown clinical efficacy, their use is often limited by systemic adverse effects. RNA interference (RNAi) offers a promising strategy for precise gene silencing, yet its therapeutic application is constrained by the poor stability and inefficient in vivo delivery of small interfering RNA (siRNA). To overcome these challenges, we developed a macrophage-targeted, colon-specific liposomal system for delivering TNF-α siRNA. The liposomes were functionalized with mannose to selectively engage the mannose receptor (MR, CD206), highly expressed on macrophages, and coated with Eudragit S100 (ES100), a pH-responsive polymer that shields siRNA from gastrointestinal degradation and enables site-specific release in the colon. The resulting ES100-coated, mannose-modified liposomes (EML/siRNA) demonstrated enhanced cellular uptake and efficient siRNA delivery to macrophages both in vitro and in vivo. In animal models of IBD, treatment with EML/siRNA significantly downregulated pro-inflammatory cytokine, alleviated intestinal inflammation, and promoted mucosal tissue repair, as evidenced by histopathological analysis. This study introduces a dual-functional nanotherapeutic platform that combines targeted RNAi-mediated TNF-α silencing with colon-specific delivery and mucosal protection, offering a promising and refined therapeutic strategy for IBD. Download: Download high-res image (159KB) Download: Download full-size image
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高影响因子
Materials Today Bio
·
2026
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IF 11
Qiusha Li,Jinglei Xu,En Zhang,Chen Liu,Wuyi Liu,Kaichuan Yan,Doudou Xu,Jian Wang
The clinical translation of RNA interference (RNAi) for lung cancer treatment remains hampered by the lack of delivery vectors that concurrently optimize cellular uptake, target specificity, and in vivo stability. This work reports an intrinsically chiral gold nanoparticle (Au NP) platform with precisely controlled morphology for targeted siRNA delivery. Through a full 2 × 2 factorial design (2 chiralities × 2 morphologies), the work decouples the individual and combined contributions of these two parameters. It is found that right-handed chiral nanoparticles (D-NPs) show significantly faster cellular internalization and higher gene silencing potency than left-handed (L-NPs) and achiral (DL-NPs) counterparts. Beyond chirality, nanoparticle morphology serves as an equally critical parameter: the rhombicuboctahedral (RCO) architecture yields markedly higher silencing efficacy than cubic counterparts with D-chirality. Furthermore, proteomic analysis revealed that Au RCO nanoparticles with different chirality displayed distinct functional enrichment profiles. By D-RCO combination with minimal surface modification, siRNA targeting PD-L1 achieves potent knockdown and robust inhibition of H460 lung cancer proliferation both in vitro and in vivo. This work establishes chirality and morphology as co-designable parameters for gene delivery and provides a mechanistic blueprint for translating chiral nanomaterials into solid tumor therapy. This work establishes intrinsically chiral Au RCO as a versatile platform for targeted siRNA immunotherapy in lung cancer. Mechanistic studies reveal that it exhibits pronounced chirality- and morphology-dependent properties, enabling efficient gene delivery and targeted gene silencing. The optimally designed D-Au RCO@mPEG@siPD-L1 nanoformulation achieves robust PD-L1 knockdown and exerts potent antitumor activity against PD-L1-high H460 cells in a T cell-independent manner. Download: Download high-res image (304KB) Download: Download full-size image
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高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
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IF 11.5
Sen Xu,Mengyu Fan,Qimeng Ding,Yibin Wang,Muhammad Ismail,Weimin Ruan,Yan Zou,Dongya Zhang,Meng Zheng
RNA interference (RNAi) has emerged as a highly promising therapeutic strategy for glioblastoma (GBM), yet its clinical efficacy heavily relies on the success of delivery systems. Traditional vehicles, including cationic polymers, lipids, and inorganic nanoparticles, frequently encounter critical challenges such as cationic toxicity, poor blood-brain barrier (BBB) penetration, or poorly-defined structures that hinder their clinical translation. To overcome these challenges, we developed a novel, structurally-defined non-cationic siRNA-micelle system based on siRNA-docosahexaenoic acid (DHA) conjugates. These conjugates self-assemble into stable siRNA-micelles that exhibit prolonged blood circulation, enhanced cellular uptake, and efficient BBB penetration. Due to their non-cationic nature and the inherent safety profile of DHA, these siRNA-DHA micelles exhibit exceptional biocompatibility, potentially minimizing carrier-based toxicity. By simultaneously targeting epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGFA), the siRNA-micelles potently inhibited tumor progression and substantially extended survival in orthotopic GBM mouse models via dual-target modulation. This structurally-defined, non-cationic siRNA delivery platform represents a robust and clinically translatable strategy for GBM treatment, and holds considerable promise for the RNAi-based therapy of other neurological disorders.
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PubMed
高影响因子
Journal of Science-Advanced Materials and Devices
·
2025
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IF 6.8
Kong Jiahui,Zhang Yongqiang,Yang Yuchang,Wang Ziheng,Jing Xiaohong,Lin Shuting,Chen Hongyue,Dong Xiaoxv,Qu Changhai,Cai Mengru,Ni Jian,Yin Xingbin
Malignant melanoma (MM) exhibits clinical traits of vigorous metastasis and an unfavorable prognosis. Traditional therapeutic modalities such as surgical resection, radiotherapy, and chemotherapy have restricted efficacy and notable side effects, thereby urgently demanding new drugs or treatment approaches. The iron-doped zeolite imidazole ester skeleton material (Fe-ZIF-8, FZ) exhibits outstanding biological safety and acid-responsive drug release properties, serving as an excellent nano-delivery carrier. Oridonin (Ori) is capable of inducing ferroptosis in tumor cells by targeting key genes (such as GPX4, SLC7A11, GGT1), and demonstrates a potent therapeutic effect on MM. Simultaneously, small interfering RNA (siRNA) can exert a role in gene silencing. In this study, we devised biomimetic nanoparticles (NPs) based on iron-doped zeolitic imidazolate framework-8 (FZ) for the co-delivery of Ori and siRNA targeting GPX4 (siRNA GPX4 ). FZ was employed to co-load Ori and siRNA targeting GPX4, the core regulator of ferroptosis, to play a role in drug and gene therapy for MM. The A375 tumor cell membrane was biomimetically modified to construct anti-tumor drug targeted delivery nanoparticles, thereby achieving efficient co-delivery of Ori and siRNA GPX4 . This provides a novel idea for the development of highly efficient and low-toxicity treatment of MM and the overcoming of tumor drug resistance.
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高影响因子
BIOMACROMOLECULES
·
2018
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IF 5.738
Zhanwei Zhou,Minghua Zhang,Yadong Liu,Chenzi Li,Qingyan Zhang,David Oupicky,Minjie Sun
Cationic polyplex as commonly used nucleic acid carriers faced several shortcomings, such as high cytotoxicity, low serum stability, and slow cargo release at the target site. The traditional solution is covering a negative charged layer (e.g., hyaluronic acid, HA) via electrostatic interaction. However, it was far from satisfactory for the deshielding by physiological anions in circulation (e.g., serum proteins, phosphate). In this study, we proposed a new strategy of reversible covalent cross-linking to enhance stability in circulation and enable stimuli-disassembly of polyplexes in tumor cells. Here, 25k polyethylenimine (PEI) was chosen as model polycations for veriying the hypothesis. HA-PEI conjugation was formed by the cross-linking of adenosine triphosphate grafted HA (HA-ATP) with phenylboronic acid grafted PEI (PEI–PBA) via the chemical reaction between PBA and ATP. Compared with noncovalent polyplex by electrostatic interaction (HA/PEI), HA-PEI exhibited much better colloidal stability and serum stability. The covered HA-ATP layer on PEI–PBA could maintain stable in the absence of physiological anions, while HA layer on PEI in HA/PEI group showed obvious detachment after anion’s competition. More importantly, the covalent cross-linking polyplex could selectively release siRNA in the ATP rich environment of cytosol and significantly improve siRNA silence. Besides, the covalent cross-linking with HA-ATP could effectively reduce the cytotoxicity of cationic polyplex, improve the uptake by B61F10 cells and promote the endosomal escape. Consequently, this strategy of HA-PEI conjugation significantly enhanced the siRNA transfection in the absence or presence of FBS (fetal bovine serum) on B16F10 cells and CHO cells. Taken together, the reversible covalent cross-linking approach shows obvious superiority compared with the noncovalent absorption strategy. It held great potential to be developed to polish up the performance of cationic polyplex on reducing the toxicity, enhancing the serum tolerance and achieving controlled release of siRNA at target site.
研究领域:
药学
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生物技术
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纳米医学
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分子生物学
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DOI
PubMed
高影响因子
EMBO JOURNAL
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2021
·Vol. 40
·期 15
·e108050
·
IF 11.598
Xin Tong,Song-Yu Liu,Jing-Ze Zou,Jia-Jia Zhao,Fei-Fan Zhu,Long-Xiang Chai,Ying Wang,Chenggui Han,Xian-Bing Wang
Selective autophagy mediates specific degradation of unwanted cytoplasmic components to maintain cellular homeostasis. The suppressor of gene silencing 3 (SGS3) and RNA-dependent RNA polymerase 6 (RDR6)-formed bodies (SGS3/RDR6 bodies) are essential for siRNA amplification in planta. However, whether autophagy receptors regulate selective turnover of SGS3/RDR6 bodies is unknown. By analyzing the transcriptomic response to virus infection in Arabidopsis, we identified a virus-induced small peptide 1 (VISP1) composed of 71 amino acids, which harbor a ubiquitin-interacting motif that mediates interaction with autophagy-related protein 8. Overexpression of VISP1 induced selective autophagy and compromised antiviral immunity by inhibiting SGS3/RDR6-dependent viral siRNA amplification, whereas visp1 mutants exhibited opposite effects. Biochemistry assays demonstrate that VISP1 interacted with SGS3 and mediated autophagic degradation of SGS3/RDR6 bodies. Further analyses revealed that overexpression of VISP1, mimicking the sgs3 mutant, impaired biogenesis of endogenous trans-acting siRNAs and up-regulated their targets. Collectively, we propose that VISP1 is a small peptide receptor functioning in the crosstalk between selective autophagy and RNA silencing.
研究领域:
植物生物学
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分子生物学
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病毒学
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遗传学
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2014
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IF 7.261
Yang Liu,Yan-Hua Zhu,Cheng-Qiong Mao,Shuang Dou,Song Shen,Zi-Bin Tan,Jun Wang
There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)- b -poly( d , l -lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NP siCDK1 ) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NP siCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer .
研究领域:
肿瘤学
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分子生物学
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药学
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纳米技术
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癌症治疗
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PubMed
高影响因子
International Journal of Nanomedicine
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2026
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IF 8.7
Zhenglu Yin,Zhaoxiang Meng,Bo Chen,Junya Wang,Aihua Zhang,Yan Shen,Xiaojia Tang,Shunyan Lin
Purpose: The clinical application of small interfering RNA (siRNA) therapy is limited by instability, inefficient tumor targeting, and inadequate responsiveness to the hypoxic tumor microenvironment. Therefore, this study aimed to construct a hypoxia-sensitive polymer-based nanocarrier to improve siRNA delivery efficiency and enhance antitumor effects in colorectal cancer (CRC).Methods: A hypoxia-sensitive polymer (mPEG-Azo-PEI) was synthesized and its cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The polymer was loaded with siRNA targeting the METTL3 gene to form nanoparticles, which were then optimized and characterized. Coumarin-loaded nanoparticles were also prepared to study the cellular uptake in HCT116 cells under hypoxic conditions. The Antitumor effects were evaluated via MTT and real-time polymerase chain reaction (RT-PCR) in vitro and in vivo, and a rectal cancer model was established using HCT116 cells in nude mice. Tumor size, weight, and histology (HE staining) were assessed, and RT-PCR analyzed METTL3 ex-pression.Results: The CMC of mPEG-Azo-PEI was 0.001687 mg/mL, indicating good self-assembly stability under dilution conditions. The optimized mPEG-Azo-PEI@siRNA2 nanoparticles exhibited a mean particle size of 141.34 ± 2.31 nm, a PDI of 0.213 ± 0.011, and a zeta potential of +21.76 ± 1.76 mV. Hypoxia-triggered release reached ~95% within 24 h, compared with ~10% under normoxic conditions. Coumarin uptake by HCT116 cells was enhanced under hypoxic conditions, indicating improved intracellular delivery. In vitro, the nanoparticles inhibited tumor cell proliferation, with IC50 values of 1.133 (normoxia) and 0.481 (hypoxia) nM. In vivo, mPEG-Azo-PEI@siRNA2 significantly suppressed tumor growth and improved body weight. RT-PCR confirmed the downregulation of METTL3, aligning with tumor suppression.Conclusion: These results demonstrated that hypoxia-sensitive mPEG-Azo-PEI@siRNA2 nanoparticles effectively delivered siRNA2 and inhibited HCT116 cell proliferation, offering a promising hypoxia-activated targeting strategy for colon cancer therapy. The graphical abstract illustrates the design and proposed mechanism of mPEG-Azo-PEI@siRNA nanoparticles for colorectal cancer treatment. In the upper section, mPEG-Azo-PEI is combined with siRNAs to form nanoparticles, with the particle size and surface charge indicated. In the lower section, HCT116 cells are used to establish a tumor-bearing mouse model. The magnified tumor schematic shows nanoparticles accumulating in the tumor microenvironment, where hypoxic conditions promote siRNA release from the carrier. The released siRNA is depicted as targeting METTL3 within tumor cells, illustrating the intended hypoxia-responsive gene-silencing strategy for antitumor therapy.Hypoxia-responsive mPEG-Azo-PEI nanoparticles for METTL3 siRNA delivery and antitumor therapy.
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高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2017
·
IF 2.31
Liangping Li,Ruisong Tao,Mingming Song,Yue Zhang,Kuanmin Chen,Hui Wang,Renmin Gong
In this paper, the starch was firstly modified by quaternary reagent to obtain cationic starch. Then self-assembled folate–biotin-quaternized starch nanoparticles were prepared by a one-pot synthesis via N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide/4-dimethylaminopyridine-mediated esterification reaction. The physicochemical properties of the prepared folate–biotin-quaternized starch nanoparticles were characterized. The average diameter of folate–biotin-quaternized starch nanoparticles was 109 nm with polydispersity index of 0.183 and zeta potential of 28.59 mV. The folate–biotin-quaternized starch nanoparticles were used as co-carrier of siRNA and doxorubicin with satisfactory drug loading capacity (6.98%) and encapsulation efficiency (69.66 %), and siRNA could be efficiently encapsulated at 40/1 weight ratio of doxorubicin/folate–biotin-quaternized starch nanoparticles to siRNA. The folate–biotin-quaternized starch nanoparticles could effectively protect siRNA from degradation of serum RNAase for up to 48 h. The release characteristics of doxorubicin and siRNA from folate–biotin-quaternized starch nanoparticles were studied in different pH environment and the release behaviors of two drugs were all pH sensitive. The folate–biotin-quaternized starch nanoparticles as a potential co-carrier of anticancer agents and gene drugs was expected to achieve future practical application in vitro and in vivo.
研究领域:
药剂学
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纳米技术
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癌症研究
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分子生物学
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PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yuhong Xiao,Yizhe He,Da Zhong,Bo Liu,ZhiBo Tang,Xiaoyong Lan,YiYang Dong,Huixian Du,Yu Liu,Jun Luo
The presence of a neurogenic bladder is a severe but common complication of spinal cord injury (SCI). Multiple pathological factors, such as hypoxia, ischemia, and oxidative stress caused by SCI, promote M1 microglial polarization and the release of proinflammatory factors to amplify inflammation. An excessive inflammatory response stimulates the generation of reactive oxygen species (ROS) and induces oxidative stress to promote neuronal ferroptosis, thus leading to bladder dysfunction after SCI. Therefore, promoting the recovery of neural function by regulating the interaction between microglia and neurons is important. For this purpose, we developed an engineered immunoregulatory cyanobacterial capsule named siRNA@Cyanzyme, which consists of MnO2@zeolitic-imidazolate framework@cyanobacteria (Cyanzyme) and a small-interfering RNA targeting ACSL4 (siRNA-ACSL4). Cyanzyme reversed M1 microglial polarization via photosynthetic oxygen to promote anti-inflammatory factor release. MnO2 nanoenzymes grown on the surface of ZIF-8 eliminated excessive ROS to reduce oxidative stress. Moreover, Cyanzyme increased the delivery efficiency of siRNA-ACSL4, which is a key regulator of ferroptosis. Both treatments alleviated GABAergic neuron damage to mitigate bladder dysfunction. Our data demonstrated that siRNA@Cyanzyme effectively reversed M1 microglial polarization, reduced neuronal ferroptosis, and ultimately restored neurogenic bladder function.
研究领域:
医学
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神经科学
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生物工程
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PubMed
高影响因子
JOURNAL OF LIPOSOME RESEARCH
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2024
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IF 3.6
Yajing Wang,Jiahui Jiang,Ziwei Ding,Tao Zhang,Yingying Shi,Xianfeng Huang,Xiaozhong Shen
ABSTACTThe medicinal properties of genetic drugs are highly dependent on the design of delivery systems. Ionizable cationic lipids are considered core materials in delivery systems. However, there has not yet been a widespread consensus on the relationship between the wide diversity of lipid structure design and gene delivery efficiency. The aims of the research work were to synthesize ionizable cholesterol derivatives (iChol-lipids) and to evaluate their potential applications as gene delivery vector. A series of iChol-lipids with different head groups were synthesized with carbamate bond spacer. The chemical structures were characterized by 1H NMR, MS, melting range, and pKa. The interactions between iChol-lipids and MALAT1-siRNA were studied by molecular dynamics simulations and compared with market available DC-Chol, which revealed that hydrogen bonds, salt-bridge, and electrostatic interaction were probably involved. The self-assemble behaviors of these lipids were intensively investigated and evaluated by dynamic laser scattering in the presence of different helper lipids and PEGylated lipids. Their plasmid binding ability, transfection efficiency, hemolytic toxicity, and cytotoxicity were fully studied. IZ-Chol-LNPs was proved to be highly potential to effectively complex with DNA, and endosome escape mechanisms mediated by proton sponge effect was verified by pH-sensitive fluorescence probe BCFL.
研究领域:
分子生物学
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药物递送系统
·
基因治疗
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PubMed
高影响因子
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