International Journal of Nanomedicine
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2025
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IF 6.5
Wenqiang Xue,Jinglei Du,Yingying Wei,Shizhao Zhou,Shicai Wang,Yongzhen Yang,Lin Chen,Shiping Yu
Background Small interfering RNA (siRNA) provides a new method for anti-tumor therapy by targeting Survivin gene in liver cancer. However, free Survivin siRNA is easily degraded and cleared by endonucleases or macrophages in the blood circulation. Therefore, it is urgent to construct a safe and efficient delivery system to achieve effective transfection of Survivin siRNA.Methods In this study, cationic carbon dots (CCDs) with active targeting ability (FA-PEI-CDs) were designed and prepared using carbon dots (CDs), polyethyleneimine (PEI), and folic acid (FA). Then, Survivin siRNA was loaded by electrostatic adsorption to design a gene-loaded complex with gene silencing effect (FA-PEI-CDs@Survivin siRNA).Results As FA-PEI-CDs had good dispersibility, an average diameter of about 21.71 nm and a zeta potential of 5.11 mV. They had good proton buffering capacity and excellent biocompatibility and could not cause erythrocyte hemolysis and thrombosis. When FA-PEI-CDs were mixed with Survivin siRNA at a mass ratio of 2:1, they can completely load siRNA without being interfered by polyanion in vivo and avoid the degradation of siRNA by serum or intracellular nuclease, which significantly increased the circulation time of siRNA in blood. Meantime, when the mass ratio of FA-PEI-CDs to Survivin siRNA was 3:1, the maximum transfection efficiency was 22.8% and 28.5% in HL-7702 cells and HepG2 cells, respectively. In vitro cell experiments confirmed that the gene complex can specifically kill tumor cells without damaging normal liver cells. In vivo tumor inhibition experiments further confirmed that FA-PEI-CDs@Survivin siRNA can cause tumor cell necrosis and reduce the expression of Survivin protein.Conclusion In summary, FA-PEI-CDs can carry Survivin siRNA to achieve tumor gene silencing therapy, which will expand the treatment of liver cancer and provide a new idea for carbon nanomaterials in biological genetic engineering.
研究领域:
医学
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遗传学
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纳米材料科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2020
·Vol. 10
·期 33
·19300-19308
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IF 3.119
Wen-Xue Lei,Zi-Shuai An,Bai-Hong Zhang,Qian Wu,Wen-Jun Gong,Jin-Ming Li,Wen-Li Chen
In recent years, gold nanoparticles (AuNPs) have been widely used as gene silencing agents and therapeutics for treatment of cancers due to their high transfection efficiency and lack of cytotoxicity, but their roles in gene silencing in plants have not yet been reported. Here, we report synthesis of AuNPs-branched polyethylenimine and its integration with the small interfering RNAs (siRNA) of NPR1 to form a AuNPs-siRNANPR1 compound. Our results showed that AuNPs-siRNANPR1 was capable of infiltrating into Arabidopsis cells. AuNPs-siRNANPR1 silenced 80% of the NPR1 gene in Arabidopsis. Bacteriostatic and ion leakage experiments suggest that the NPR1 gene in Arabidopsis leaves was silenced by AuNPs-siRNANPR1. In Columbia-0 plants, compared with the control group treated with buffer solution, the AuNPs-siRNANPR1 treatment significantly increased the number of colonies and cell death, and the leaves turned yellow, similar to the phenotype of the npr1 leaves. These results indicated this AuNPs-siRNANPR1 silencing the NPR1 gene method is simple, effective and quick (3 days), and a powerful tool to study gene functions in plants.
研究领域:
植物科学
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分子生物学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Small
·
2023
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IF 13.3
Huimin Xu,Jianqiao Chang,Hao Wu,Haoyu Wang,Wenjing Xie,Yunchao Li,Xiaohong Li,Yang Zhang,Louzhen Fan
Small interfering RNA (siRNA)-based gene therapy represents a promising strategy for tumor treatment. Novel gene vectors that can achieve targeted delivery of siRNA to the tumor cells without causing any side effects are urgently needed. To this end, the large amino acid mimicking carbon dots with guanidinium functionalization (LAAM GUA-CDs) are designed and synthesized by choosing arginine and dopamine hydrochloride as precursors. LAAM GUA-CDs can load siRNA through the multiple hydrogen bonds between their guanidinium groups and phosphate groups in siRNA. Meanwhile, the amino acid groups at the edges of LAAM GUA-CDs endow them the capacity to target tumors. After loading siBcl-2 as a therapeutic agent, LAAM GUA-CDs/siBcl-2 has a high tumor inhibition rate of up to 68%, which is twice more than that of commercial Lipofectamine 2000. Furthermore, LAAM GUA-CDs do not cause side effect during antitumor treatment owing to their high tumor-targeting ability, thus providing a versatile strategy for tumor-targeted siRNA delivery and cancer therapy.
研究领域:
生物医学工程
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分子生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Kai Yu,Lidan Fu,Yu Chao,Xiaodong Zeng,Yonggang Zhang,Yuanyuan Chen,Jialu Gao,Binchun Lu,Hua Zhu,Lijuan Gu,Xiaoxing Xiong,Zhenhua Hu,Xuechuan Hong,Yuling Xiao
Small interfering RNA (siRNA) targeting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as a promising therapeutic strategy to mitigate infarct volume and brain injury following ischemic stroke. However, the clinical translation of siRNA-based therapies is significantly hampered by the formidable blood-brain barrier (BBB), which restricts drug penetration into the central nervous system. To address this challenge, we have developed an innovative long-circulating near-infrared II (NIR-II) nanoparticle platform YWFC NPs, which is meticulously engineered to enhance BBB transcytosis and enable efficient delivery of siRNA targeting NLRP3 (siNLRP3@YWFC NPs) in preclinical models of ischemic stroke. Furthermore, we integrated advanced deep learning neural network algorithms to optimize in vivo NIR-II imaging of the cerebral infarct penumbra, achieving an improved signal-to-background ratio at 72 h poststroke. In vivo studies employing middle cerebral artery occlusion (MCAO) mouse models demonstrated that image-guided therapy with siNLRP3@YWFC NPs, guided by prolonged NIR-II imaging, resulted in significant therapeutic benefits.
研究领域:
神经科学
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药理学
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医学影像学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
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IF 8.758
Shengyu Zhang,Ye Gan,Lanlan Shao,Tianqing Liu,Danyi Wei,Yanyan Yu,Hongwei Guo,Hongyan Zhu
Targeting vascular endothelial growth factor (VEGF) using small interfering RNA (siVEGF) has shown great potential in inhibiting the growth, proliferation, and migration of tumors by reducing the proliferation of blood vessels. On the basis of bionic principles, a novel pH-responsive and virus mimetic shell-sheddable chitosan (CS) micelles (CMs) as siRNA delivery system was introduced in this study. The cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) modified poly(enthylene glycol) (PEG) was conjugated to the HA2 modified chitosan via a hydrazone linkage (cRGD-PEG-Hz-CS-HA2). The cRGD-PEG-Hz-CS-HA2 conjugate could form micelles by interacting with the complex of octanal, Boc-l-lysine, and 9-d-arginine (9R) (octyl-Lys-9R) as a hydrophodic core forming agent, termed as cRGD-PEG-Hz-CS-HA2/octyl-Lys-9R (abbreviated as cRGD/HA2/Hz-CMs).The CMs modified with cRGD can accurately target glioma cells (U87MG cells) with high expression of αvβ3. The payloads of siVEGF were packed into the core of cRGD/HA2/Hz-CMs via electrostatic interaction and hydrophobic interaction. The intracellular cargo release was achieved by the pH-responsive lysis of the hydrazone bond in acidic environment of endosome. Moreover, the exposed HA2, as a pH-sensitive membrane-disruptive peptide, assists the escape of the carriers from endosome into cytosol. In addition, cRGD/HA2/Hz-CMs can effectively deliver siVEGF and silence VEGF gene expression in U87MG cells, leading to the significant tumor growth inhibition. This study demonstrates that cRGD/HA2/Hz-CMs can deliver and release siVEGF in a controlled manner, which was traced by the fluorescence resonance energy transfer (FRET) system in order to achieve RNAi-based anti-angiogenic treatment of cancer in vivo.
研究领域:
药剂学
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分子生物学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 35
·5910-5924
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IF 0
Hongmei Liu,Chenmeng Qiao,Jun Yang,Jie Weng,Xin Zhang
Co-delivery of siRNAs and chemotherapeutic drugs to kill tumors have achieved superior tumor growth inhibition. However, due to siRNAs and chemotherapeutic drugs with different molecular properties, co-delivery carriers use more cationic materials to bind siRNAs and excessive inert materials to embed drugs, causing low drug-loading contents and systemic toxicity. To achieve this goal, doxorubicin (DOX) is chemically conjugated to stearoyl chloride (C18) through N-methyldiethanol amine (N) as cross-linker to form amphiphilic C18–N–DOX. C18–N–DOX contains a tertiary amine that can complex siRNAs at low pH (pH 3) and reduce the density of the positive charges on the surface of NPs at physiological pH (pH 7.4). C18–N–DOX, together with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) DSPE-PEG2000, self-assemble into DOX-prodrug nanoparticles (DOX-prodrug NPs), which bind siRNAs in citrate buffer (pH 3) to form DOX-prodrug NPs/siRNA. After replacing citrate buffer (pH 3) with PBS (pH 7.4), DOX-prodrug NPs/siRNA have slight negative charges due to complexed more siRNAs. In this study, clear evidence is shown that DOX-prodrug NPs can deliver siRNA to the same tumor cells both in vitro and in vivo. Moreover, DOX-prodrug NPs/siRNA show a great effect on inhibiting tumor cell growth both in vitro and in vivo. Therefore, the DOX-prodrug NPs are promising candidates as siRNAs delivery system for tumor therapy.
研究领域:
药理学
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癌症研究
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2017
·Vol. 18
·期 10
·2029
·
IF 3.226
Hongyan Zhu,Wanwan Liu,Ziting Cheng,Ke Yao,Yu Yang,Bohui Xu,Gaoxing Su
In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose (DG) is the targeting molecule, polyethylene glycol (PEG) helps to improve the dispersity and biocompatibility, 9-poly-d-arginine (9R) is employed to provide a positive surface charge and adsorb negative siRNA, and hydrazone bonds are pH-responsive and can avoid receptor-mediated endosomal recycling. Compared to GNS alone, 9R/DG-GNS (hydrazone) showed superior transfection efficiency. The expressions of cyclooxygenase-2 (COX-2) in HepG2 and SGC7901 cells were significantly suppressed by siRNA/9R/DG-GNS (hydrazone) complex. Notably, 9R/DG-GNS (hydrazone) possessed low cytotoxicity even at high concentrations in both normal cells and tumor cells. The combination treatment of siRNA/9R/DG-GNS (hydrazone) complex inhibited the cell growth rate by more than 75%. These results verified that the pH-responsive GNS complex is a promising siRNA delivery system for cancer therapy, and it is anticipated that near-infrared absorbing GNS with good photothermal conversion efficiency can be potentially used for photothermal therapy of tumors.Keywords:gold nanostars;targeted delivery;siRNA;cancer treatment;cyclooxygenase-2;gene silence
研究领域:
纳米技术
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癌症生物学
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
PLANT CELL
·
2024
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IF 10
Wu Xinyang,Chen Shuting,Zhang Zixin,Zhou Weixin,Sun Ting,Ning Kang,Xu Min,Ke Xubo,Xu Pei
Virus-induced drought tolerance presents a fascinating facet of biotic-abiotic interaction in plants, yet its molecular intricacies remain unclear. Our study shows that cowpea mild mottle virus (CPMMV) infection enhances drought tolerance in common bean (Phaseolus vulgaris) plants through a virus-derived small interfering RNA (vsiRNA)-activated autophagy pathway. Specifically, a 21-bp vsiRNA originating from the CPMMV Triple Gene Block1 (TGB1) gene targeted the 5' untranslated region (UTR) of the host Teosinte branched 1, Cycloidea, Proliferating Cell Factor (TCP) transcription factor gene PvTCP2, independent of the known role of TGB1 as an RNA silencing suppressor. This targeting attenuated the expression of PvTCP2, which encodes a transcriptional repressor, and in turn upregulated the core autophagy-related gene (ATG) PvATG8c, leading to activated autophagy activity surpassing the level induced by drought or CPMMV infection alone. The downstream EARLY RESPONSIVE TO DEHYDRATION (ERD) effector PvERD15 is a homologue of Arabidopsis thaliana AtERD15, which positively regulates stomatal aperture. PvERD15 was degraded in PvATG8c-mediated autophagy. Therefore, we establish a TGB1-PvTCP2-PvATG8c-PvERD15 module as a trans-kingdom fine-tuning mechanism that contributes to virus-induced drought tolerance in plant-drought-virus interactions.
研究领域:
植物病毒学
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分子生物学
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植物生理学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 15
·期 4
·4177-4184
·
IF 1.664
Zhengting Chen,Xinyi Cai,Li Chang,Yaoxiong Xia,Li Wang,Yu Hou,Lan Li,Dingguo Pan,Furong Li,Shan Liu,Wei Xiong,Wenhui Li
Concurrent radiotherapy and chemotherapy is a widely used, comprehensive treatment for rectal cancer. By studying the impact of concurrent chemoradiotherapy on the invasion and migration of colorectal cancer (CRC) cells and researching the associated molecular mechanisms, the present study aimed to provide a novel method to improve the therapeutic effect of this treatment against CRC. Human HCT116 and HT29 CRC cells were simultaneously treated with 4 Gy of 6 MV X‑rays and 10 µmol/l 5‑fluorouracil to establish a residual cell model. Transwell migration and invasion experiments were used to analyse the invasion and migration of the cells. The expression of long non‑coding (lnc)RNAs was detected using a gene chip, and reverse transcription‑quantitative polymerase chain reaction analysis was used to determine lncRNA expression levels. Specific small interfering RNAs were transfected into HCT116 residual cells to silence the expression of the identified key genes. The migration and invasion of residual CRC cells were demonstrated to be significantly increased compared with the original cells. Pvt1 oncogene, long‑chain non‑protein‑coding RNA 152 (LINC00152), and MIR22 host gene were selected as potential targets. However, the migration and invasion of residual HCT116 cancer cells were only significantly decreased following silencing of LINC00152 expression. LINC00152 may therefore be a potential biomarker involved in modulation of the biological characteristics of residual CRC cells following chemoradiotherapy.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Jove-Journal of Visualized Experiments
·
2019
·
IF 1.108
Na Jia,Haoan Wu,Juanli Duan,Chunxue Wei,Kaixuan Wang,Yu Zhang ,Xiaohua Mao
Because of their critical role in regulating immune responses, macrophages have continuously been the subject of intensive research and represent a promising therapeutic target in many disorders, such as autoimmune diseases, atherosclerosis, and cancer. RNAi-mediated gene silencing is a valuable approach of choice to probe and manipulate macrophage function; however, the transfection of macrophages with siRNA is often considered to be technically challenging, and, at present, few methodologies dedicated to the siRNA transfer to macrophages are available. Here, we present a protocol of using polyethyleneimine-coated superparamagnetic iron oxide nanoparticles (PEI-SPIONs) as a vehicle for the targeted delivery of siRNA to macrophages. PEI-SPIONs are capable of binding and completely condensing siRNA when the Fe:siRNA weight ratio reaches 4 and above. In vitro, these nanoparticles can efficiently deliver siRNA into primary macrophages, as well as into the macrophage-like RAW 264.7 cell line, without compromising cell viability at the optimal dose for transfection, and, ultimately, they induce siRNA-mediated target gene silencing. Apart from being used for in vitro siRNA transfection, PEI-SPIONs are also a promising tool for delivering siRNA to macrophages in vivo. In view of its combined features of magnetic property and gene-silencing ability, systemically administered PEI-SPION/siRNA particles are expected not only to modulate macrophage function but also to enable macrophages to be imaged and tracked. In essence, PEI-SPIONs represent a simple, safe, and effective nonviral platform for siRNA delivery to macrophages both in vitro and in vivo.
研究领域:
免疫学
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纳米医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 28
·5597-5607
·
IF 4.543
Gerile Gerile,Tsogzolmaa Ganbold,Yizheng Li,Huricha Baigude
Intracellular delivery of genetic material is a potentially powerful therapeutic approach for the treatment of genetic diseases. However, the scarcity of biocompatible delivery systems is a tremendous barrier for the application of nucleic acid therapy in the clinic. Herein, we successfully created biocompatible nucleic acid delivery systems based on cationic lipids consisting of alternatively linked ornithine residues in the head group (denoted DoGo lipids). Transfection of the pcDNA3-eGFP plasmid into cells using DoGo lipids resulted in significant transfection efficiency without showing any apparent cytotoxicity. Meanwhile, DoGo lipids efficiently delivered siRNA to cancer cell lines and induced profound RNAi activity at a siRNA concentration as low as 5 nM. DoGo lipid driven delivery of a siRNA against polo-like kinase 1 (Plk1) in cancer cells induced significant morphological changes in the cell and the nucleus due to cell cycle arrest and inhibition of cell proliferation, a phenotype resulting from the decreased Plk1 protein level. Our findings demonstrate that DoGo lipids have great potential in clinical application for gene based therapy.
研究领域:
分子生物学
·
基因工程
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药物学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Weijie Li,Ruicong Yan,Yong Liu,Chuanchuan He,Xiaojuan Zhang,Yao Lu,Muhammad Waseem Khan,Chuanrui Xu,Tan Yang,Guangya Xiang
Overexpression of Bmi1 gene is an important feature of cancer stem cell in various human tumors. Therefore, Bmi1 gene can be a potential target for small interfering RNA (siRNA) mediated cancer therapy. Ursolic acid (UA) as a natural product plays a pivotal role in anti-tumor field, although its performance is limited by low bioavailability and poor hydrophilicity. A folate receptor-targeted cationic liposome system was designed for the purpose of investigating the relationship between Bmil siRNA and UA. The folate receptor-targeted cationic liposomes co-delivering UA and Bmi1 siRNA (FA-UA/siRNA-L) were fabricated by electrostatic interaction between folate UA liposome (FA-UA-L) and Bmi1 siRNA. Tumor growth is inhibited by FA-UA/siRNA-L in vitro and in vivo and this inhibition is contributed by a synergistic anti-tumor effect of UA and Bmi1 siRNA. The western blot measurement of apoptosis-protein and cancer stem cell (CSC) marked-protein demonstrated that UA led to activation-induced tumor cell death and Bmi1 siRNA resulted in inhibition of cancer stem cells. Overall, these results indicate that Bmi1 as a regulating gene for cancer stem cell is an effective target for cancer treatment using siRNA and co-delivery of UA and Bmi1 siRNA using folate-targeted liposomes is a promising strategy for improved anti-tumor effect.
研究领域:
肿瘤学
·
药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）