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
·
癌症生物学
·
分子生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 19
·期 5
·3658-3666
·
IF 1.851
Jin Xu,Yin Ying,Gaoyun Xiong,Liqin Lai,Qingliang Wang,Yue Yang
Nasopharyngeal carcinoma (NPC) is a type of cancer originating in the nasopharynx. There are no NPC‑specific treatments available at present. Serpin peptidase inhibitor clade C member 1 (SERPINC1) serves roles in anticoagulation and anti‑inflammation. The aim of the present study was to investigate the role of SERPINC1 in the proliferation and apoptosis of NPC cells. Tumor and adjacent healthy tissue samples were collected from patients with NPC. Additionally, the SERPINC1 gene was silenced in the HNE3 cell line using short interfering RNA targeted against SERPINC1 (SERPINC1‑siRNA). Cell viability was determined via a Cell Counting Kit‑8 assay; furthermore, proliferation and apoptosis were investigated via flow cytometry. Western blotting and reverse transcription‑quantitative polymerase chain reaction analysis were performed to determine the expression levels of protein and mRNA. It was revealed that the expression levels of SERPINC1 mRNA and protein were increased in NPC tumor tissues compared with in adjacent healthy tissues. The expression of SERPINC1 mRNA and protein in HNE3 cells decreased following SERPINC1‑siRNA transfection. Furthermore, knockdown of SERPINC1 promoted apoptosis and inhibited proliferation. It was also demonstrated that silencing SERPINC1 upregulated the expression of B‑cell lymphoma-2 (Bcl‑2)‑associated X protein and p53 mRNA and protein, and downregulated that of Bcl‑2, survivin and cyclin D1. Downregulation of SERPINC1 reduced the phosphorylation of phosphatidylinositol 3‑kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Thus, SERPINC1 knockdown may promote the apoptosis of HNE3 cells and inhibit proliferation via the suppression of the PI3K/Akt/mTOR signaling pathway.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yi Chen,Wei Chen,Yiming Ren,Yanjie Zhang,Zhaoqi Tan,Wenzhe Huang,Xueshan Bai,Liya Yang,Shuyun Liu,Quanyi Guo,Li Teng
Impaired efferocytosis in diabetic wounds contributes to apoptotic cell accumulation, chronic inflammation, and poor healing outcomes. In this study, a multi-hierarchical hydrogel designed to facilitate cellular debridement and initiate a healing process in diabetic wounds is proposed. A reactive oxygen species (ROS)/glucose-responsive hydrogel conjugated with chemokine aptamers is developed that encapsulated mannose-modified lipid nanoparticles (mLNPs) loaded with ADAM17 siRNA (A disintegrin and metalloproteinase 17). This hydrogel enhanced macrophage recruitment by enriching endogenous chemokines. Additionally, it responded to the pathological microenvironment, enabling the dynamic release of mLNPs for targeted siRNA delivery to macrophages. Treatment with ADAM17 siR@mLNPs significantly enhanced macrophage efferocytosis through the MerTK-Rac1 pathway and glycolytic reprogramming, thereby initiating the resolution of inflammation and tissue repair. Finally, in animal models of diabetic wounds, this therapy reduced the apoptotic burden and improved wound healing. In conclusion, macrophage-targeted efferocytosis-reactivation therapy is a promising strategy for the treatment of diabetic wounds.
研究领域:
医学
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生物材料学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOTECHNOLOGY AND BIOPROCESS ENGINEERING
·
2015
·Vol. 20
·期 3
·550-560
·
IF 1.113
Hao Shanhu,Yan Ying,Ren Xue,Xu Ying,Chen Lanlan,Zhang Haibo
A multifunctional polymer-drug conjugate candesartan-graft-polyethyleneimine (CD-PEI, CP) containing low molecular weight polyethyleneimine (PEI) and candesartan (CD) conjugated via an amide bond was fabricated as a co-delivery micelle of drug and siRNA for potential lung cancer therapy. Here, CD as an angiotensin II type 1 receptor blocker rich in imidazole and tetrazole rings was utilized to strengthen endosomal buffering capacity of CP and suppress tumor angiogenesis. The selfassembled CP/siRNA complexes exhibited desirable and homogenous particle size, moderate positive charges, and efficient release of drug and siRNA in vitro . In addition, CD and siRNA could readily detached from nanovectors in tumor cells via an amidase-responsive mechanism and they achieved synergistic anti-angiogenesis efficacy by effectively downregulating the expression of vascular endothelial growth factor (VEGF) mRNA and protein via different pathways in vitro. In vivo investigation on nude mice bearing A549 tumor xenografts revealed that CP/siRNA complexes possessed strong antitumor activity. These findings suggested that CP could be an ideal nanovector for simultaneous transfer of drug and siRNA, and a multifunctional CP/siRNA co-delivery system with enhanced endosomal buffering capacity, amidase-responsive drug release and synergistic anti-angiogenesis efficacy might be a new promising strategy for effective lung cancer therapy.
研究领域:
药学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
高影响因子
PHYSIOLOGICAL RESEARCH
·
2023
·
IF 2.1
T Wang,Q Wang,G Pan,G Jia,X Li,C Wang,L Zhang,C Zuo
The acidic tumor microenvironment (TME) of pancreatic cancer affects the physiological function of pancreatic stellate cells (PSCs), which in turn promotes cancer progression. Acid-sensing ion channel 1a (ASIC1a) is responsible for acidosis-related physiopathological processes. In this study, we investigated the effect of acid exposure on the activation and autophagy of PSCs, and the role of ASIC1a in these events. The results showed that acidic medium upregulated the expression of ASIC1a, induced PSCs activation and autophagy, which can be suppressed by inhibiting ASIC1a using PcTx1 or ASIC1a knockdown, suggesting that ASIC1a involves these two processes. In addition, the acid-induced activation of PSCs was impaired after the application of autophagy inhibitor alone or in combination with ASIC1a siRNA, meaning a connection between autophagy and activation. Collectively, our study provides evidence for the involvement of ASIC1a in the acid-caused PSCs activation, which may be associated with autophagy induction.
研究领域:
肿瘤学
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Yunchun Zhao,Caihong Zheng,Li Zhang,Yue Chen,Yiqing Ye,Mengdan Zhao
Biodegradable and biocompatible poly( d,l -lactic- co -glycolic acid) (PLGA)was conjugated to the 5′-thiol end of signal transducer and activator of transcription 3 (STAT3) small interfering RNA (STAT3–siRNA) via a disulfide bond. In aqueous environments, these siRNA–PLGA conjugates can spontaneously form core/shell type spherical micelles with a particle size of about 200 nm. A biodegradable, low molecular weight cationic polymer, chitosan oligosaccharide (CSO), was added to the siRNA–PLGA micelles at different nitrogen to phosphate (N/P) ratios to form stable, spherical siRNA–PLGA/CSO micelles with sizes of 150–180 nm. The siRNA–PLGA/CSO micelles were produced via ionic complexation between negatively charged siRNA and positively charged CSO on the outer shell of the micelles. The siRNA–PLGA/CSO micelles exhibited superior cellular uptake and STAT3 gene silencing efficiency in SKOV3 ovarian cancer cells when compared with siRNA/CSO complexes at the same N/P ratios with no significant differences with lipofectamine 2000. Furthermore, the siRNA–PLGA/CSO micelles showed that the efficiencies of cellular uptake and STAT3 gene silencing gradually increased with increasing N/P ratios. The siRNA–PLGA/CSO micelles also inhibited the growth of SKOV3 cells, as well as, promoted apoptosis of the cells. These results indicate that siRNA–PLGA/CSO micelles can be utilized as a novel and efficient siRNA carrier to treat a variety of diseases.
研究领域:
癌症研究
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药学
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纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Zhiyu Su,Tseyenkhorloo Erdene-Ochir,Tsogzolmaa Ganbold,Huricha Baigude
Developing nucleic acid-based tools to control disease-relevant gene expression in human disorders, such as siRNAs, opens up potential opportunities for therapeutics. Because of their high molecular weight and polyanionic nature, synthetic siRNAs fail to cross biological membranes by passive diffusion and therefore, generally require transmembrane siRNA delivery technologies to access the cytoplasm of target cells. To create a biocompatible siRNA delivery agent, we chemically modified natural polysaccharide curdlan derivative 6AC-100 in a regioselective manner to introduce different ratios of imidazole rings in the amino units (denoted as Curimi) and evaluated their siRNA binding ability, cytotoxicity, endosome buffering capacity and siRNA transfection efficiency. The novel curdlan based Curimi polymers formed nanoparticles with siRNA at pH 7.4 in range of 85–105 nm and their size distribution increased along with decreasing pH condition. The zeta potential increased by lowering pH value as well. Curimi polymers showed lower toxicity and higher buffering capacity compared to 6AC-100, and efficiently delivered siRNA against to PLK1 into cancer cells, and subsequently, significantly inhibited target mRNA level. Our result suggested that novel curdlan based Curimi polymers may be used as efficient siRNA carrier for cancer therapy.
研究领域:
生物技术
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药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2023
·
IF 2.9
Dianwen Yu,Hui Wang,Hui Liu,Rong Xu
Triple-negative breast cancer (TNBC), which accounts for 10%–20% of breast cancer cases, is characterized by a higher metastasis rate, higher recurrence risk, and worse prognosis. Traditional treatments such as chemotherapy, surgery, and radiotherapy have limited therapeutic effects. Although immune checkpoint blockade (ICB) therapy represented by anti-programmed death 1 (aPD-1) antibody has made further progress in treating TNBC, its therapeutic effect is still not optimistic. Ataxia telangiectasia mutated (ATM) is a critical factor in the DNA damage response (DDR) pathway, which is associated with the development of tumors. Recent studies have found that it can regulate the tumor immune microenvironment, affecting ICB responsiveness. Inhibition of ATM could enhance ICB therapy by promoting mitochondrial DNA cytoplasmic leakage and activating the innate immune signaling pathway. To explore the effect of ATM siRNA(siATM) on the ICB responsiveness of TNBC, we designed and synthesized nanoparticles using 1,2-dioleoyl-glycero-3-phosphatidylcholine (DOPC) liposomes to deliver siATM. In vitro and in vivo experiments demonstrated that DOPC/siATM could enhance the ability of siRNA to enter tumor cells and effectively inhibit the expression of ATM protein. Our study found that nanoparticles carrying siATM could activate cytotoxic T lymphocytes and regulate the immunosuppressive tumor microenvironment (ITM) by activating the cGAS-STING pathway. Its combination with aPD-1 may be a potential way to improve the efficacy of TNBC.
研究领域:
肿瘤学
·
免疫治疗
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分子生物学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 39
·6468-6474
·
IF 4.872
Wanwan Shen,Hui Wang,Ye Ling-hu,Jia Lv,Hong Chang,Yiyun Cheng
RNA interference has significant potential as an important tool in biology and medicine. For the development of highly efficient non-viral siRNA carriers, hydrophobic modification on cationic polymers has received increasing attention. Here, we described the screening of efficient siRNA carriers in a library of hydrophobically modified polyethyleneimines (PEIs). Cationic PEI was grafted with hydrophobic ligands including alkanes, cycloalkanes and fluoroalkanes. These modifications significantly improved the gene knockdown efficacy of PEI. Among the functionalized polymers, the fluoroalkylated PEIs showed higher efficacies and lower toxicities than the alkylated and cycloalkylated ones. The top performing polymers in the library efficiently knocked down several target genes in different cell lines without off-target effects. The revealed structure–activity relationships of alkylated, cycloalkylated and fluoroalkylated PEIs in this study provide a new insight into the design of highly efficient and non-toxic siRNA carriers.
研究领域:
生物技术
·
药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Mingming Zhang,Xi Zhang,Sijun Huang,Yueming Cao,Yi Guo,Li Xu
Paclitaxel (PTX) is commonly used in clinical tumor therapy. However, chemoresistance and the inducement of tumor metastasis severely affect the efficacy of PTX. To develop a treatment strategy to reverse chemoresistance, the co-delivery of PTX and small interfering RNA with nanocarriers were programmed in this study. The carrier we have programmed exhibits excellent safety, stability, and delivery efficiency for co-delivery of siRNA and PTX. After rapid release of siRNA, PTX could be released within 72 h. The siBcl-xL and siMcl-1 inhibited cell migration decreased the mitochondrial membrane potential , and induced the release of reactive oxygen species while synergistically functioning with the antineoplastic effects of PTX. Our strategy reduced IC 50 values by 2–5-fold in different cell lines, and the results of flow cytometry confirmed increased apoptosis rates and effectively inhibited cell migration. Synergistic therapy effectively reversed chemoresistance in PTX-resistant breast cancer cells. Similarly, the synergistic administration strategy showed significant sensitizing effects in vivo. Our study demonstrates the combined application of multiple synergistic antitumor administration strategies.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Zhouchun Chen,Qingshan Yang,Mengyu Fan,Tianran Chai,Yang Liu,Xue Xia,Muhammad Ismail,Meng Zheng
Targeting mitochondrial-mediated energy metabolism has emerged as a promising therapeutic strategy for glioblastoma multiforme (GBM), given its crucial role in sustaining the rapid growth and survival of tumor cells. In this study, we developed a combinatory, non-cationic siRNA-conjugated self-assembled micelle system core-encapsulated with Gboxin (siRNA-micelle@Gboxin) designed to induce severe mitochondrial dysfunction in GBM cells. The mTOR-siRNA component in the micelle silences mTOR expression, downregulates mTORC1 activity, and reduces 4EBP1 phosphorylation, leading to inhibition of mRNA translation and disruption of cellular energy metabolism, ultimately resulting in decreased ATP production. Concurrently, the GBM-specific drug Gboxin inhibits oxidative phosphorylation (OXPHOS), directly inducing mitochondrial dysfunction and exacerbating the energy crisis within glioma cells, synergistically accelerating apoptosis through mitochondrial damage. Notably, this dual-target inhibition of mTORC1 and OXPHOS by siRNA-micelle@Gboxin resulted in a more potent, synergistic anti-tumor effect than targeting either pathway alone. These findings highlighted that the Gboxin-loaded siRNA micelle offers a promising and innovative nanotherapeutic approach for GBM treatment, harnessing the synergistic effects of gene silencing and chemotherapy-based mitochondrial disruption to achieve a powerful therapeutic efficacy.
研究领域:
肿瘤学
·
纳米医学
·
分子生物学
·
癌症代谢
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Zekun Wang,Ruofei Zhang,Yanyu Hu,Qile Song,Xiaoyan Fu,Yifan Wang,Mei Chen,Kelong Fan,Cundong Fan,Dongdong Sun
Doxorubicin (DOX) treatment can lead to intracellular iron overload in cardiomyocytes, triggering excessive generation of reactive oxygen species (ROS) and resulting in cardiotoxicity. Superoxide dismutase (SOD) effectively scavenges ROS, and its catalytic activity depends on the binding of metal ions at its active site. Therefore, enhancing the activity of metal-dependent SOD represents a promising strategy to inhibit ferroptosis in cardiomyocytes and alleviate DOX-induced chronic heart failure. In this study, we constructed a biomimetic chiral MnO 2 nanozyme co-modified with macrophage and platelet membranes (D/L-MnO 2 @MM), enabling precise targeting of DOX-injured myocardial tissues. This nanozyme exhibited potent catalase-like and SOD-like activities, efficiently eliminating excessive local hydrogen peroxide (H 2 O 2 ) and superoxide anions (O 2 •− ). Notably, the D-enantiomeric nanozyme (D-MnO 2 @MM) significantly enhanced endogenous SOD2 activity via Mn 2+ ion release, thereby suppressing the accumulation of lipid peroxides. Furthermore, based on transcriptomic and proteomic analyses, we designed an siRNA targeting the Hmox1 gene (si Hmox1 ) and successfully loaded it onto the nanozyme platform (si Hmox1 @D/L-MnO 2 @MM). Both in vitro and in vivo experiments confirmed that the dual mechanism, SOD2 activation and Hmox1 silencing, effectively restored mitochondrial function, attenuated ferroptosis, and significantly improved cardiac function in a rat model of chronic heart failure. Collectively, this study proposes a novel ferroptosis-targeted therapeutic strategy based on a biomimetic chiral nanozyme, offering new insights and promising therapeutic potential for the treatment of DOX-induced cardiotoxicity.
研究领域:
心血管病学
·
纳米医学
·
分子生物学
·
药理学
·
氧化应激
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基因治疗
·
转化医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）