Advanced Science
·
2026
·
IF 14.1
Yaosheng Li,Yunfei Dong,Yaode He,Juanjuan Zheng,Hui Liu,Lu Li,Xiaoxu Hao,Yanli Zhao,Zefeng Yang,Yuankai Sun,Zhiwei Du,Bo Zhao,Weihang Zhou,Honghui Wu,Tianyuan Zhang,Jiahe Wu,Xiangrui Liu,Xianzhen Yin,Zhicai Chen,Rui Xue,Min Lou,Zhen Gu,Xinchi Jiang,Jianqing Gao
Changes in the blood-brain barrier (BBB) are key targets for mitigating cerebral ischemia/reperfusion injury. The rapid progression of reperfusion injury necessitates the development of carriers that target and regulate early BBB disruption, while supporting its structure and function during BBB recovery. This study proposes the use of brain microvascular endothelial cell (mECs)-based vascular bandages carrying siRNAs to simultaneously target, support, and regulate the damaged BBB. Specifically, mECs can target damaged cerebral blood vessels after intravenous injection by interacting with the highly expressed very late antigen - 4 (VLA-4) in the vessels. Furthermore, by covering the cerebral blood vessels and forming new junction proteins with the vascular endothelium, mECs support the permeability and structural integrity of the vasculature. Additionally, oxygen-glucose deprivation-treated mEC culture supernatants (OGD-SN) can promote connexin 43 (CX43) expression, facilitating the delivery of therapeutic p66 Shc siRNA to the damaged endothelium for BBB regulation. Ultimately, vascular bandage treatment rescued BBB function, alleviated reperfusion injury, and reduced the infarct area. Our study offers a new therapeutic strategy and a novel brain-targeted delivery platform for treating cerebral ischemia/reperfusion injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Xiang Yu,Ze Meng Ma,Feng Ji,Mingjiu Chen,Huricha Baigude
Antibody–siRNA conjugate (ARC) is a novel therapeutic strategy developed based on the concept of antibody–drug conjugate (ADC). It combines the targeting specificity of antibodies with the gene silencing ability of small interfering RNA (siRNA) and shows broad application prospects. However, the development of traditional ARC in the field of tumor treatment faces many challenges, and the DNA Topoisomerase I Inhibitor-Exatecan is limited in its clinical application due to its strong hydrophobicity and significant toxicity. In this study, we developed a novel antibody–siRNA–Exatecan conjugate (AREC). By introducing siRNA, we plan to increase the hydrophilicity of small molecule drugs and optimize the drug to antibody ratio (DAR) to 1 and 2. This modification not only significantly reduced the toxic side effects associated with high DAR values, but also provided a basis for evaluating the synergistic anti-tumor effect between STAT3 gene silencing and Exatecan. In vitro experimental results showed that AREC can efficiently kill tumor cells, fully demonstrating its great potential as a multifunctional platform for tumor targeted therapy.
研究领域:
肿瘤学
·
分子靶向治疗
·
药物递送系统
·
生物偶联化学
·
RNA干扰
·
制药生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Feifei Yang,Wei Huang,Yunfei Li,Shan Liu,Mingji Jin,Yuli Wang,Lihua Jia,Zhonggao Gao
Recently, survivin has been attracting great attention because it plays an important role in inhibiting the apoptosis process of tumor cells. Down-regulating the expression of survivin gene by small interfering RNA (siRNA) offers a promising method for anti-tumor therapy. However, lack of appropriate siRNA delivery vector has significantly hindered the successful application of survivin-targeted siRNA in anti-tumor therapy. The purpose of this study was to use polysaccharide vector TAT-g-CS we synthesized to deliver functional siRNA and evaluate its in vivo anti-tumor activity. TAT-g-CS vector was firstly synthesized and well structurally characterized. MTT assay showed that TAT-g-CS vector exhibited good biocompatibility . TAT-g-CS complexed with siRNA offering nanoparticles with an average particle size of 212.2 nm and a polydispersity index of 0.121, and the zeta potential of the nanoparticles was +18.58 mV. Results from reporter gene assay suggested that luciferase-targeted siRNA when delivered by TAT-g-CS could down-regulate the expression of luciferase gene with 75.3% reduction. Most importantly, we use siRNA Sur targeting survivin gene to assess the in vitro and in vivo delivery capacity of TAT-g-CS and its anti-tumor effects. Our results demonstrated that TAT-g-CS/siRNA Sur nanoparticles not only strongly inhibited the in vitro proliferation of 4T1-Luc tumor cells via inducing cell apoptosis, but also effectively inhibited the in vivo growth and metastasis of malignant breast tumor, which suggested that TAT-g-CS/siRNA nanoparticle was a highly efficient non-viral system for siRNA delivery, especially for anti-tumor therapy based on siRNA therapeutics.
研究领域:
癌症生物学
·
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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Di Wu,Jiebing Yang,Zhen Xing,Haobo Han,Tingting Wang,Aijun Zhang,Yan Yang,Quanshun Li
In this study, the conjugation of phenylboronic acid (PBA) to amine-terminated polyamidoamine (PAMAM) was successfully conducted to prepare a tumor-targeted gene carrier PBA-functionalized PAMAM (PPP) for Bcl-2 siRNA delivery, using a heterobifunctional crosslinker NHS-PEG 5k -Mal. The carrier possessed favorable capacity for siRNA condensation and could protect siRNA from the degradation against RNase and serum. The introduction of PBA could facilitate the cellular uptake and further transfection of Bcl-2 siRNA demonstrated by confocal laser scanning microscopy and flow cytometry. Meanwhile, PPP-mediated transfection of Bcl-2 siRNA could significantly inhibit the expression of Bcl-2 gene at both mRNA and protein levels. Furthermore, owing to the knock-down of Bcl-2, PPP/siRNA could significantly inhibit the cell proliferation by inducing the cell apoptosis, and also enhance the antitumor efficiency of doxorubicin by suppressing the resistance of tumor cells to chemotherapeutics. In conclusion, the PPP-mediated Bcl-2 siRNA delivery could potentially be an effective platform for solving the drug resistance and further achieving the combined chemotherapy and gene therapy in tumor treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2016
·Vol. 5
·期 5
·584-592
·
IF 5.76
Chongyi Liu,Naimin Shao,Yitong Wang,Yiyun Cheng
Cationic dendrimers are widely used as nonviral gene vectors, however, current gene materials based on dendrimers are either little effective or too toxic on the transfected cells. Here, a facile strategy is presented to prepare high efficient dendrimers with low transfection toxicity. Small dendrimers with 2 nm are clustered into nanoaggregates (≈100 nm) via phenylboronic acid modification and the self-assembled materials enable efficient DNA and siRNA delivery on several cell lines. The clustered nanostructures can disassemble into small dendrimers in acidic conditions thus exerting significantly less toxicity on the transfected cells. Further structure–function relationship studies reveal that both the phenyl group and boronic acid group play essential roles in the self-assembly and gene delivery processes. The transfection efficacy of phenylboronic acid-modified dendrimers can be down-regulated by blocking the boronic acid groups on dendrimers with diols or degrading the groups with hydrogen peroxide. This study provides a facile strategy in the development of efficient and biocompatible gene vectors based on low molecular weight polymers and clearly demonstrates the structure–function relationship of phenylboronic acid-modified polymers in gene delivery.
研究领域:
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Fangyu Qiao,Yang Zou,Binglin Bie,Yonggang Lv
Vascularization and innervation play irreplaceable roles in bone regeneration and bone defect repair. However, the reconstruction of blood vessels and neural networks is often neglected in material design. This study aims to design a genetically functionalized matrix (GFM) and enable it to regulate angiogenesis and neurogenesis to accelerate the process of bone defect repair. The dual small interfering RNA (siRNA)-polyvinylimide (PEI) (siRP) complexes that locally knocked down soluble vascular endothelial growth factor receptor 1 (sFlt-1) and p75 neurotrophic factor receptor (p75 NTR ) are prepared. The hybrid cell membrane (MM) loaded siRP is synthesized as siRNA@MMs to coat on polylactone (PCL) electrospun fibers for mimicking the natural bone matrix. The results indicates that siRNA@MMs could regulate the expression of vascular-related and neuro-related cytokines secreted by mesenchymal stem cells (MSCs). GFMs promote the expression of osteogenic differentiation through paracrine function in vitro. GFMs attenuates inflammation and promotes osseointegration by regulating the coupling of vascularization and innervation in vivo. This study uses the natural hybrid cell membrane to carry genetic material and assist in the vascularization and innervation function of two siRNA. The results present the significance of neuro-vascularized organoid bone and may provide a promising choice for the design of bone tissue engineering scaffold.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2021
·
IF 3.517
Xue Li,Shuxin Xu,Haojiang Wang,Anjie Dong
For the past few years, organic-inorganic hybrid nanocarriers have been widely explored for effective drug delivery and preferable disease treatments. In this article, hydrothermal method was utilized to prepare fine dispersed layered double hydroxide (Mg-Al LDH) suspension. Polyethylene glycol (PEG) was grafted on the surface of LDH lamella in order to improve the dispersibility of LDH. Besides, the anti-cancer drug gemcitabine was grafted on the surface of LDH lamellas through chemical grafting. Hence a novel new type of organic-inorganic hybrid drug delivery system LDH-mPEG-Gemcitabine was obtained. In addition, the siRNA was intercalated into the LDH interlamination by ion exchange method to realize drug and gene co-delivery. The loading capacity of LDH and LDH-mPEG-Gemcitabine was evaluated by agarose gel electrophoresis. The characterization by laser particle size analyzer, TEM, FT-IR, XRD, in vitro cell viability and in vitro drug release demonstrated that LDH-mPEG-Gemcitabine possessed fine dispersibility, uniform morphology and particle size, fine biocompatibility, ideal drug loading and releasing capacity and held great potential to be used as a desired co-delivery system for drug and gene.
研究领域:
药剂学
·
生物材料学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Jingwen Liu,Liang Chen,Zhenyu Sun,Zaijin Tao,Volotovski Pavel,Yusheng Li,Fei Wang,Wenguo Cui,Shen Liu
Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.
研究领域:
生物医学工程
·
组织工程
·
基因治疗
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2019
·
IF 0
Jiantao Yu,Jing Li,Shiyao Zhai,Li Lin,Kui Wang,Bin Tang,Hong Meng,Leilei Tian
Polymerization of small interfering RNA (siRNA) has been demonstrated as a promising strategy to improve siRNA delivery, which will change the low-charge and rigid properties of single siRNA and enhance its electrostatic interactions with cationic polymers. For such polymerization strategy, a major breakthrough is still needed to fully eliminate chemical processes and further improve the nanocomplex-forming ability of polymerized siRNAs. Herein, the extremely strong interaction between the DNA product of rolling circle amplification (RCA) and linear poly(ether imide) (PEI) has been disclosed; accordingly, a stable nanocomplex is formed just at its charge neutralization point, which benefits from the high molecular weight of the RCA product (>3 000 000 Da). In addition, as the sequence of the RCA product is determined by the cyclic template, the programmable nature of DNA can simplify the optimization process and maximize the hybridization efficiency between RCA and sticky siRNAs, realizing a superior siRNA polymerization efficiency. Depending on these two effects, the RCA DNA is utilized as a cocarrier material to organize siRNA polymerization and substantially reduce the usage amount of PEI, which greatly improves RNAi efficiency of PEI/RCA-siRNA polyplex both in vitro and in vivo, providing evidence that RCA DNA is a promising material to promote the RNAi-based therapeutics.
研究领域:
分子生物学
·
纳米医学
·
治疗开发
✓ 已验证
产品关联
DOI
PubMed
Biomaterials Advances
·
2022
·
IF 0
Ruimin Tang,Chunsheng Shao,Liangjian Chen,Li Yi,Bo Zhang,Jiangjie Tang,Weina Ma
Osseointegration between implants and bone tissue lays the foundation for the long-term stability of implants. The incorporation of a porous structure and local slow release of siRNA to silence casein kinase-2 interacting protein-1 (CKIP-1), a downregulator of bone formation, is expected to promote osseointegration. Here, porous implants with a porous outer layer and dense inner core were prepared by metal coinjection molding (MIM). Mg-doped calcium phosphate nanoparticles (CaPNPs)-grafted arginine-glycine-aspartate cell adhesion sequence (RGD) and transcribed activator (TAT) (MCPRT)/CKIP-1 siRNA complex and polylysine (PLL) were coated onto the surface of the porous implants by layer-by-layer (LBL) self-deposition. The in vitro results showed that the MCPRT-siRNA coating promoted MG63 cell adhesion and proliferation, enhanced the protein expressions (ALP and OC) and bone formation-related gene expression (OPN, OC and COL-1α) in vitro. The in vivo results demonstrated that the porous structure enhanced bone ingrowth and that the local slow release of MCPRT-siRNA accelerated new bone formation at the early stage. The porous structure coupled with local CKIP-1 siRNA delivery constitutes a promising approach to achieve faster and stronger osseointegration for dental implants.
研究领域:
生物材料
·
生物医学工程
·
骨科
·
组织工程
✓ 已验证
DOI
PubMed
STAR Protocols
·
2026
·Vol. 7
·期 4
·104854
·
IF 1.4
Yan Fang,Jianfeng Shen
Steps for preparing LIN28B siRNA-loaded nanoparticles • Procedures for establishing a murine malignant ascites model • Instructions for administering nanoparticles and PARP inhibitors in vivo • Methods for assessing tumor burden and vascular permeability Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Summary Malignant serous effusion (MSE) is a life-threatening complication of advanced cancers with limited effective treatments. Here, we present a protocol for the preparation of LIN28B siRNA-loaded nanoparticles and their combination with PARP inhibition for therapeutic evaluation in malignant ascites (MA). We describe steps for nanoparticle formulation, establishment of murine ascites models, and in vivo administration of therapeutic agents. We then detail procedures for assessing tumor progression, vascular permeability, and endothelial junction integrity to evaluate treatment efficacy and microenvironmental remodeling. For complete details on the use and execution of this protocol, please refer to Fang et al. 1 Download: Download high-res image (221KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
ACS Applied Nano Materials
·
2026
·
IF 5.8
Liu Kai,Shen Hongliang,Li Jietao,Feng Yu,Zhou Chang,Jiang Anlong
Osteosarcoma remains a highly aggressive primary bone
malignancy,
and its clinical treatment is frequently limited by chemoresistance,
systemic toxicity, and insufficient tumor-specific drug accumulation.
To address these challenges, we developed an OS-7.9 aptamer-functionalized
ZIF-8 nanoscale platform for the targeted codelivery of sorafenib
(SFN) and GPX4 siRNA, designated O-SR-ZIF-8, with the intended application
of ferroptosis-based osteosarcoma therapy. The resulting nanoparticles
exhibited a uniform nanoscale size distribution, favorable colloidal
stability, high payload-loading capacity, and pH-responsive release
behavior. The ZIF-8 nanostructure remained relatively stable under
physiological conditions but promoted accelerated release of SFN and
GPX4 siRNA in acidic tumor-mimicking microenvironments, supporting
its suitability for tumor-localized delivery. Compared with nontargeted
formulations, O-SR-ZIF-8 markedly enhanced cellular internalization
in MG-63 osteosarcoma cells, inhibited cell proliferation, promoted
cell death, increased intracellular oxidative stress, and suppressed
migration and invasion. In a murine osteosarcoma xenograft model,
systemic administration of O-SR-ZIF-8 significantly restrained tumor
growth through GPX4 silencing and modulation of ferroptosis-related
signaling. Moreover, the nanoscale formulation exhibited favorable
biocompatibility, as evidenced by negligible hemolytic activity and
no obvious histopathological injury in major organs. Together, these
findings indicate that O-SR-ZIF-8 is an aptamer-guided nanoscale therapeutic
platform with potential in the treatment of osteosarcoma through targeted
delivery of sorafenib and GPX4 siRNA to silence genes and increase
oxidative stress associated with ferroptosis.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）