NPG Asia Materials
·
2020
·Vol. 12
·期 1
·1-11
·
IF 8.131
Yuan Zihan,Guo Xiaoshuang,Wei Minyan,Xu Yang,Fang Zhiwei,Feng Yun,Yuan Wei-En
Small-interfering RNA (siRNA) can specifically silence disease gene expression, bringing hope for the effective treatment of gene-related diseases. However, its use in vivo is limited due to the lack of efficient carriers. Therefore, it is necessary to construct carriers with high efficiency, low toxicity and serum stability. As a promising polycation carrier, polyethylenimine (PEI) can be further modified with a fluorine-containing alkyl chain that brings hydrophobic and oleophobic characteristics to its surface. In this study, low molecular weight PEI 1.8 kDa was selected and fluorinated through an anhydride reaction, and the product was named PEIF. In vitro experiments have shown that PEIF/siRNA polyplexes have suitable and stable particle size and potential, compress nucleic acids at a very low w / w ratio, and have the ability to effectively silence specific genes with low cytotoxicity. Compared with the polyplexes prepared using PEI 25 kDa, the PEIF/siRNA polyplexes were more stable in serum, showed a better antiangiogenic ability in in vivo experiments, and had a better tumor inhibition effect. The above results indicate that fluoropolymers based on the fluorine effect have great potential as gene delivery carriers for tumor therapy.
研究领域:
药学
·
分子生物学
·
癌症研究
·
基因治疗
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Jiaoyu Ren,Yanyan Cuan
Excessive iron ion accumulation in cells can trigger apoptosis; however, the balance of iron ions in cells minimizes the effect of excessive iron accumulation. Here, we report a biocompatible nanomotor that reduces the ability of cells to clear iron ions using loaded siRNA. First, catalase and polydopamine were loaded onto Fe 3 O 4 particles by layer-by-layer self-assembly technology to endow the particles with a self-propulsion ability. A nanomotor (NP-siRNA) loaded with siRNA was then prepared by electrostatic action. Nanoparticles (NP) can achieve self-actuation in an aqueous solution with a magnetic field and H 2 O 2 and have good movement ability in water, PBS, and FBS solutions, resulting in greater contact with tumor cells. The results show that the nanomotor has good in vivo and in vitro anti-tumor effects, and good biocompatibility.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
分子生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 38
·7623-7630
·
IF 4.726
T. Y. Cheang,Z. H. Xing,Z. L. Li,H. Y. Zhou,J. H. Wei,X. Zhou,A. W. Xu,Y. Lin,S. M. Wang
Here, a novel carrier fabricated by the interaction of negatively charged heparin and positively charged PEI and Ca2+ was investigated to deliver AIB1 siRNA into breast cancer cells both in vitro and in vivo. Ca2+/PEI/heparin nanoparticles were prepared by simply mixing heparin, PEI and CaCl2 aqueous solution. Heparin in the Ca2+/PEI/heparin nanoparticles (40.9% heparin, w/w) decreased the cytotoxicity of PEI. According to the MTT assay, Ca2+/PEI/heparin NPs are superior to commercial Lipofectamine 2000 considering the safety. The Ca2+/PEI/heparin NPs are able to deliver siAIB1 into breast cancer cells as effectively as Lipofectamine 2000 both in vitro and in vivo. The in vivo experiment also indicated that the NF-κB/BCL-2 signal pathway might be the downstream signal pathway of AIB1 in regulating breast cancer proliferation and progression.
研究领域:
癌症研究
·
纳米技术
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yufeng Zhang,Yini Huangfu,Ling Xu,Zhezhe Zhao,Qi Su,Hui Li,Yumin Zhang,Chuangnian Zhang,Pingsheng Huang,Anjie Dong,Zujian Feng,Weiwei Wang
Antimicrobial-resistant (AMR) Gram-negative bacteria emerge due to the overuse of antibiotics. Moreover, current bactericidal drugs or materials inevitably associate with the immunologic risks from the lipopolysaccharide (LPS) released by dead bacteria, which initiates and exacerbates chronic tissue-destructive hyperinflammation, leading to treatment failure. In this study, we describe an orchestrated pH-sensitive cationic polymer nanoparticle encapsulated with rifampicin and toll-like receptor (TLR) siRNA (RNP/siRNA) that exhibits antibacterial and LPS-detoxifying characteristics for treating infected diseases. Under acidic conditions, RNP/siRNA nanoparticle releases rifampicin and cationic polymers displaying synergistically inhibitory activity against AMR bacteria by disrupting bacterial membranes, and facilitating the entry of antibiotics. Furthermore, RNP/siRNA nanoparticle exhibits high cellular uptake and TLR knockdown efficiency, thereby detoxifying the etiological LPS in M1-type macrophages polarization and reducing proinflammatory cytokines. In a mouse pneumonia model, RNP/siRNA nanoparticle treatment inhibits bacterial growth, suppresses inflammation and reduces leukocyte recruitment. In a rat periodontitis model, the administration of RNP/siRNA downregulates proinflammatory cytokines expression and inhibits bone resorption. This work highlights the elevated LPS release is an early trigger of hyperinflammation during the antibacterial process of currently established antimicrobials. The RNP/siRNA nanoparticle represents a promising strategy by integrating antibiosis and immunomodulation in a cascading manner for the treatment of bacterial infections.
研究领域:
医学
·
药学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Cuihua Zhang,Yawen Yao,Wenqiu Xu,Jieying Zhou,Hua Yu,Ying Li,Wei Xiong
Efficient cytosolic delivery of small interfering RNA (siRNA) remains a challenge in RNA therapeutics, particularly for oral administration. Identifying new cytosolic stimulus-responsive targets is thus crucial for optimizing siRNA delivery. Given the elevated intracellular arginase-1 (Arg1) levels in inflamed colonic mucosa, we developed lipid nanoparticles (siRNA-LANPs) derived from L-arginine-modified chitosan (ACS) for the cytosolic release of TNF-α-siRNA to treat ulcerative colitis (UC). The siRNA-LANPs exhibited superior Arg1-binding affinity compared to its substrate, L-arginine, enabling rapid Arg1-responsive release. Moreover, we found that siRNA-LANPs maintained nanoparticle stability, and 84.5 % of the loaded siRNA remained intact in simulated digestive fluids over 12 h. Following oral administration, siRNA-LANPs efficiently penetrated the mucus layer and preferentially accumulated in inflamed colonic tissue compared to healthy colon tissue. In DSS-induced colitis mice, siRNA-LANPs significantly reduced disease severity through TNF-α silencing, achieving greater therapeutic efficacy than sulfasalazine (a first-line UC treatment). The siRNA-LANPs exhibited superior TNF-α silencing compared to transfection reagent Lipo3000 and TNF-α biologic agent infliximab. The enhanced performance was attributed to multiple endocytic pathways, improved lysosomal escape capability (29.7 %), and Arg1-mediated cytoplasmic siRNA release. In summary, Arg1 seems to be a promising intracellular target for stimulus-responsive, oral siRNA delivery in UC treatment.
研究领域:
RNA治疗
·
纳米医学
·
胃肠病学
·
药物递送
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-16
·
IF 9.429
Liu Qiqi,Zhang Ying,Huang Jingkai,Xu Zhourui,Li Xiang,Yang Jingyu,Huang Haoqiang,Tang Shiqi,Chai Yujuan,Lin Jinbo,Yang Chengbin,Liu Jia,Lin Suxia
The colonization of bacterial pathogens is a major concern in wound infection and becoming a public health issue. Herein, a core–shell structured Ag@MSN (silver core embedded with mesoporous silica, AM)-based nanoplatform was elaborately fabricated to co-load ciprofloxacin (CFL) and tumor necrosis factor-α (TNF-α) small interfering RNA (siTNF-α) (AMPC@siTNF-α) for treating the bacterial-infected wound. The growth of bacterial pathogens was mostly inhibited by released silver ions (Ag + ) and CFL from AMPC@siTNF-α. Meanwhile, the loaded siTNF-α was internalized by macrophage cells, which silenced the expression of TNF-α (a pro-inflammatory cytokine) in macrophage cells and accelerated the wound healing process by reducing inflammation response. In the in vivo wound model, the Escherichia coli (E. coli) -infected wound in mice almost completely disappeared after treatment with AMPC@siTNF-α, and no suppuration symptom was observed during the course of the treatment. Importantly, this nanoplatform had negligible side effects both in vitro and in vivo. Taken together, this study strongly demonstrates the promising potential of AMPC@siTNF-α as a synergistic therapeutic agent for clinical wound infections. Graphical Abstract
研究领域:
纳米技术
·
药学
·
生物医学工程
·
传染病
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Zhipeng Yang,Yanjie Liu,Haoyuan Li,Qisheng Tang,Biao Yang,Zhifeng Shi,Ying Mao
The blood–brain barrier (BBB) and drug resistance present challenges for chemotherapy of glioblastoma (GBM). A microneedle (MN) patch with excellent biocompatibility and biodegradability was designed to bypass the BBB and release temozolomide (TMZ) and PLCG1-siRNA directly into the tumor site for synergistic treatment of GBM. The codelivery of TMZ and PLCG1-siRNA enhanced DNA damage and apoptosis. The potential mechanism behind this enhancement is to knockdown of PLCG1 expression, which positively regulates the expression of signal transducer and activator of transcription 3 genes, thereby preventing DNA repair and enhancing the sensitivity of GBM to TMZ. The MN patch enables long-term sustainable drug release through in situ implantation and increases local drug concentrations in diseased areas, significantly extending mouse survival time compared to other drug treatment groups. MN drug delivery provides a platform for the combination treatment of GBM and other central nervous system diseases.
研究领域:
药学
·
神经科学
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2023
·
IF 4.6
Qidi Ren,Lu Wang,Wenfei Qian,Baiqiu Chen,Qi Shuai,Yunfeng Yan
RNA interference (RNAi) is a promising approach for disease treatments. But the development of safe and effective delivery carriers remains a major challenge. Organic–inorganic hybrid nanoparticles (NPs), with the integration of functions from distinct materials, show great potential in small interfering RNA (siRNA) delivery. Herein, pH responsive amorphous calcium carbonate NPs (ACC NPs) are prepared using flash nanoprecipitation and hybrid NPs are constructed by coating ACC NPs with polyethyleneimine (PEI) for efficient siRNA delivery. PEI/ACC NPs show robust pH responsiveness and stability as well as effective siRNA loading and protection. Furthermore, siRNA-loaded PEI/ACC NPs demonstrate enhanced cellular uptake and efficient endosomal escape, mediating improved siRNA delivery compared to pure PEI. These findings suggest that PEI/ACC NPs may have great potential in siRNA delivery for RNAi-based therapy.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 57
·33302-33309
·
IF 3.049
Yanhua Zhang,Hui Huang,Hao Fu,Meng Zhao,Zhihua Wu,Yang Dong,He Li,Yourong Duan,Ying Sun
As known to all, ovarian cancer ranks the most lethal of the gynecological malignancies. The antitumor drugs based on platinum are first-line chemotherapy drugs for ovarian cancer. However, their therapeutic efficiency is severely limited owing to dose-limiting toxicities of platinum. New theranostic strategies to overcome chemotherapy toxicity is highly desirable. Meanwhile, the real-time treating effect is not visible for doctors. Herein, we constructed PFH/siRNA/Fe3O4@Pt(IV) NPs-cRGD (NPs-cRGD) for precise theranostics against ovarian tumors with real-time imaging. The NPs-cRGD had a good storage stability and resisted the serum-induced aggregation, which was beneficial for drug delivery. Additionally, gel-retardation assay demonstrated that the NPs-cRGD exhibited great protection to siRNA to resist nuclease degradation. In vitro, the NPs-cRGD showed good dual-mode US/MRI imaging and the relative imaging research was also discussed. Moreover, the in vitro experiments indicated that the NPs-cRGD with US exhibited excellent antitumor therapeutic efficiency, resulting from the cRGD ligands and US exposure enhanced the cellular uptake efficiency. Thus, the dual-mode nanoparticles in this work may provide precious insight into the development of various multi-mode nanoplatforms delivering drugs or genes for precise theranostics against various cancer.
研究领域:
癌症治疗
·
纳米医学
·
医学影像
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Danni Liu,Yaoqi Wang,Qi Sun,Dong Mei,Xiaoling Wang,Yan Su,Jie Zhang,Ran Huo,Yang Tian,Siyu Liu,Shuang Zhang,Chunying Cui
Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.
研究领域:
癌症治疗
·
纳米技术
·
基因递送
·
细胞生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 21
·2008960
·
IF 18.808
Jiandong Yang,Shanzhou Duan,Huan Ye,Chenglong Ge,Chunxian Piao,Yongbing Chen,Minhyung Lee,Lichen Yin
Pulmonary delivery of anti-inflammatory siRNA holds great potential in mitigating the cytokine storm during severe pneumonia. However, commonly utilized polycationic siRNA delivery vehicles can hardly penetrate the mucus barrier, thus greatly hurdling their therapeutic efficacy. Herein, TNF-α siRNA (siTNF-α) delivery nanocomplexes (NCs) are engineered with mucus/cytomembrane dual-penetration capabilities, realized via surface-coating of NCs with RC, an inflammation-sheddable, charge-reversal pro-peptide of RAGE-binding peptide (RBP). RC-coated dendritic poly- L -lysine/siTNF-α (DsT) NCs possess negative surface charges, and can thus efficiently penetrate the mucus layer after intratracheal administration. In the inflamed alveolar space with mild acidity, RC recovers to the cationic RBP and shed off, re-exposing the DsT NCs that efficiently transfect the alveolar macrophages and provokes TNF-α silencing. Thus, siTNF-α and RBP cooperatively alleviate the uncontrolled inflammation during acute lung injury. This study renders a unique approach for mediating trans-mucus nucleic acid delivery, and will find promising utilities for the treatment of severe pneumonia.
研究领域:
药剂学
·
纳米技术
·
肺科学
·
分子生物学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Zhanwei Zhou,Chenzi Li,Minghua Zhang,Qingyan Zhang,Chenggen Qian,David Oupicky,Minjie Sun
Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA. In this study, we propose a new strategy by the combination of micelles disassembly and separated polycations charge reversal. FPBA (3-fluoro-4-carboxyphenylboronic acid) grafted PEI 1.8 k (polyethylenimine) as the polycations of PEI-FPBA and dopamine (with diol-containing moiety) conjugated with cholesterol as the hydrophobic part (Chol-Dopa). The PFCDM micelles was assembled by PEI-FPBA and Chol-Dopa, based on the FPBA-Dopa conjugation. The prepared PFCDM showed strong siRNA loading ability and superior stability in the presence of PBS or serum. Besides, the PFCDM exhibited excellent ATP sensibility. The intracellular ATP could effectively trigger the disassembly of micelles and charge reversal of PEI-FPBA, resulting in the burst release of siRNA in the cytosol. With the property of extracellular stability and intracellular instability, PFCDM displayed good performance on in vitro and in vivo luciferase silencing on 4T1 cells. It should also be noted that the assembly of low molecular weight PEI was relatively safe to cells compared with 25 k PEI. To sum up, the ATP-fueled assembly and charge reversible micelles gave examples for polyplexes to achieve better stability and on demand cargo release at the same time and shows potential to be used for in vitro and in vivo siRNA transfection.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
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）