Journal of Macromolecular Science Part A-Pure and Applied Chemistry
·
2019
·
IF 1.163
Jie Wang,Songyan Liu,Ying Chang,Le Fang,Kai Han,Miao Li
Nowadays development of safe and simple siRNA delivery system is still a great challenge. Carbon dots have attracted considerable attention in bioimaging, drug delivery, nanosensors, and other fields during the past few years. In this study, we successfully developed carbon dots (TEPA-CDs) as siRNA nanocarriers based on glucose and tetraethylene pentamine. TEPA-CDs have a mean diameter of less than 10 nm and positive charged decoration. TEPA-CDs could condense siRNA into stable complexes without no obvious premature release. Cellular uptake analysis clearly showed that Cy3-labeled siRNA could be uptake by HeLa cells. GFP expression in HeLa-EGFP cells could be significantly inhibited by TEPA-CDs/siRNA complexes. Our study indicated that TEPA-CDs could be used as a siRNA nanocarrier to tumor cells.
研究领域:
纳米技术
·
分子生物学
·
癌症研究
·
药物递送
·
生物成像
✓ 已验证
DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-20
·
IF 15.7
Cui Lele,Cui Yongsheng,Liu Jing,Li Wei,Wu Mengdan,Wei Xiawei,Lai Ying,Mi Peng
A major obstacle in knocking down oncogenes for tumor therapy is the efficient delivery of siRNA into the cytosolic spaces of cancer cells. Here, we genetically bioengineer biomimetic nanovesicles with tumor-recognition and enzyme-controlled membrane fusion functions for efficiently delivering small interfering RNA into cancer cells towards gene silencing tumor therapy. The siRNA@eS-BNVs are formulated by encapsulating siRNA inside the core and coating with genetically engineered HEK293T ACE2- cell membranes encoded with functional S protein, which can recognize cancer cells and initiate membrane fusion when triggered by the enzyme. The siRNA@eS-BNVs demonstrate better efficacy for cytosolic siRNA delivery and RNA interference than conventional formulations. By intravenous injection, siRNA@eS-BNVs are highly accumulated in tumors and potently inhibited tumor and lung metastasis by simultaneously silencing the epidermal growth factor receptor gene in vivo. The cancer cell-targeting and enzyme-activatable nanovesicles provide a valuable strategy for effective and precise drug delivery.
研究领域:
生物工程
·
肿瘤学
·
分子生物学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Tsogzolmaa Ganbold,Shuqin Han,Agula Hasi,Huricha Baigude
Natural carbohydrate polymer-based nanoparticles have great biocompatibility that is required for the safe delivery of various drugs including nucleic acid therapeutics. Herein, we designed curdlan-based nanoparticles for cancer cell targeted delivery of short interfering RNA (siRNA). iRGD peptide conjugated 6-amino-6-deoxy curdlan specifically delivered siRNA to integrin expressing cancer cells. Incubation of cancer cells with free iRGD peptide competitively blocked cellular uptake of the iRGD functionalized curdlan nanoparticles. Chloroquine but not nystatin inhibited cellular uptake of iRGD functionalized curdlan nanoparticles, indicating that the iRGD peptide conjugated curdlan nanoparticles were internalized through the receptor (clathrin)-mediated endocytosis. Moreover, a disease related gene Plk1 was substantially knocked down by siRNA carried by 6AC-iRGD nanoparticles in HepG2 cells. Our data suggested that iRGD functionalized curdlan may provide a biocompatible carrier for siRNA delivery.
研究领域:
生物医学工程
·
分子生物学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 11
·3075-3084
·
IF 5.831
Qiong Sun,Chunming Tang,Zhigui Su,Junjie Du,Yunkai Shang,Lingjing Xue,Can Zhang
Cationic lipids and polymers are the most common non-viral vectors for siRNA delivery; however, their intense positively charged character may give rise to serum-triggered aggregation, immune activation, inflammation stimulation and grievous toxicity. An ocean of charge shielding strategies is exploited, but the currently available siRNA delivery systems still remain ungratified and deficient. Herein, we developed a facile modular assembly strategy for a pH-sensitive charge reversal siRNA delivery system (PC), which can be easily obtained by adjusting the ratios of positively and negatively charged modules. This PC is electronegative at neutral pH and reverses to electropositive at an acidic pH value with increased tumor cellular uptake. Also, the PC can promote efficient intracellular release and cytoplasmic distribution of siRNA, due to its fusogenic potential with the lysosome membrane. Moreover, the PC loaded with siRNA targeting survivin mRNA (cpusiRNA2) specifically down-regulated the expression of survivin, possessing remarkable tumor therapeutic efficacy in vitro and in vivo. Accordingly, this handy and effective assembly strategy would provide a promising platform for the design of siRNA delivery systems in cancer therapy.
研究领域:
生物技术
·
药学科学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 5
·964
·
IF 6.525
Yingying Zhang,Hongxia Duan,Heming Zhao,Lingling Qi,Yanhong Liu,Zheao Zhang,Chao Liu,Liqing Chen,Mingji Jin,Youyan Guan,Zhonggao Gao,Wei Huang
Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways.Keywords:prostate cancer;androgen receptor;siRNA delivery;docetaxel;PSMA targeting
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2013
·
IF 3.458
Gaoyang Guo,Li Zhou,Zhifei Chen,Weilin Chi,Xiuqun Yang,Wei Wang,Biliang Zhang
Small interfering RNA (siRNA) has tremendous potential as a therapeutic agent for diverse diseases; however, due to its susceptibility to degradation and poor cellular uptake, the low efficiency of administration has been the most important limiting factor for clinical applications of siRNA. Herein, we synthesized alkyl chain modified low-molecular-weight polyethylenimines (LMW PEIs) and found that hydrophobically modified PEIs displayed enhanced efficiency in siRNA-mediated knockdown of target genes. To elucidate the mechanism for increased delivery, we characterized the polymers’ physicochemical properties and bioactivity via nuclear magnetic resonance (NMR), gel retardation assay, dynamic laser scattering (DLS) analysis, confocal laser scanning microscopy and flow cytometry. The hydrophobic modification reduced siRNA binding affinity but facilitated the formation of nanoparticles in contrast to the original PEI. The PEIs with eight and thirteen alkyl tails were able to self-assemble into nanoparticles and yielded higher cellular uptake, which leaded to even similar efficiencies of 80–90% knockdown as Lipofectamine™ 2000 control. These results suggested that the status of polymers in aqueous solution, which depended on the degree of hydrophobic modification, played an important role in the uptake of siRNA. Therefore, we provided new information on the role of hydrophobic content in the enhanced gene silencing activity.
研究领域:
分子生物学
·
基因治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
TECHNOLOGY AND HEALTH CARE
·
2016
·
IF 0.678
Zhang Yujuan,Song Na,Fu Jiamin,Liu Yanling,Yu Yanrong,Shi Qiaofa,Fu Yingyuan,Zhou Nanjing,Yuan Keng,Zhao Lin,Zhang Quan,Min Weiping
RNA interference (RNAi) employs double-stranded RNA or
siRNA (small interfering RNA) to silence gene expression in cells. The
widespread use of RNAi therapeutics requires the development of clinically
suitable, safe and effective delivery vehicles. PEI (Poly(ethylene imine))
carrying the positive charges has attracted considerable attention for siRNA
delivery. Gold nanorods (GNRs) exhibit specially localized surface plasmon
resonance when excited by the visible and near-infrared laser, which is
useful for photothermal therapy. However, the toxicity derived from a large
amount of the surfactant cetyltrimethylammonium bromide (CTAB) during GNR
synthesis severely limits their medical applications. Here, we report the
synthesis of GNRs-PEI/GNRs-PEI-folate to improve biocompatibility, siRNA
delivery and photothermal therapy of GNRs. Firstly, GNRs were synthesized
according to the seed-mediated template-assisted protocol. The
characterization results of GNRs showed: the size was length about 218 nm
and width about 26.8 nm; the Zeta potential was +38.1 mV derived from CTAB
on their surface; the dipole resonance extinction spectrum peak was 752 nm
which is effective for photothermal therapy in vivo. Secondly, we
synthesized PEI-MUA (Mercaptoundecanoic acid) and PEI-MUA-folate based on
the chemical reaction between amino group of PEI and carboxyl group of MUA
or Folate. PEI-MUA or PEI-MUA-folate to replace CTAB on GNRs obtained the
GNRs-MUA-PEI system or the GNRs-MUA-PEI-folate system due to the solid
conjugation between the thiol group of MUA and GNRs. The products were
measured using the FTIR Spectrometer, and the spectra suggest MUA-PEI or
PEI-MUA-folate has successfully replaced CTAB on the surface of GNRs.
Finally, GNRs-MUA-PEI was incubated with siRNA-Cy3. The unbound siRNA-Cy3
was measured the intensity of fluorescence for calculating the uploaded
amount of siRNA by GNRs-MUA-PEI, and the results indicate that the uploaded
percentage of siRNA is about 70%. We conclude that the GNRs-MUA-PEI
system is an effective siRNA loading vehicle.
研究领域:
纳米医学
·
基因治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Yan Zhang,Qin LiMiao,Feng MengFan,Xianghui Yu,Yuqing Wu
Small interfering RNA (siRNA), comprising 21-23 nucleotides, functions by complementary binding to specific mRNA sequences, thereby suppressing target protein expression. Despite their vast potential in disease therapy, siRNAs face challenges due to their susceptibility to degradation and high electronegativity, rendering them unstable in the bloodstream and impeding their passage across endothelial barriers. Moreover, successful intracellular delivery necessitates overcoming endosomal entrapment, posing a significant hurdle for carrier material development. In this study, leveraging the strong affinity of histidine oligomers (His6) for metal ions, we engineered nanoparticles (HmA) by gentle assembly with divalent zinc ions under pH=8 conditions. We designed the RNA-binding functional peptide L2-NTD to enhance siRNA stability and delivery efficiency when complexed with HmA. The resulting siRNA+L2-NTD@HmA nanoparticles were formed via in situ encapsulation, ensuring efficient siRNA delivery into cells with minimal cytotoxicity and degradation. This approach presents a novel strategy for the design and artificial fabrication of carriers for effective RNA delivery.
研究领域:
分子生物学
·
药物递送
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Yuxuan Qi,Yiwen Pan,Feng Gu,Shuai Wei,Chenglong Fei,Jingfen Han
RNA interference technology is a powerful tool with substantially clinical prospects for carcinoma therapy, in which efficiency and specificity of delivery of dsRNA remains a critical issue. Herein, aiming at delivery of dsRNA in efficient and safe way, we constructed targeting delivery platform (CTL-PEG-FA) by grafting curdlan with trilysine through click reaction, then modifying with PEG linked folic acid. The CTL-PEG-FA vector exhibited excellent gene binding capacity to condense siRNA and dramatically reduced cytotoxicity. Increased cell uptake of CTL-PEG-FA/Bcl-2 siRNA was achieved by the synergism of folate mediated endocytosis and charge interaction, and further causing severe HepG2 cells injury through apoptosis mechanism after down-regulation of Bcl-2 protein. In vivo experiments, CTL-PEG-FA/Bcl-2 siRNA complex distinctly accumulated in tumor site and significantly inhibited the growth of tumor, while no obvious toxicity was observed. Therefore, well-performed CTL-PEG-FA with excellent biocompatibility, has the potential to be the candidate of gene therapy for clinical applications.
研究领域:
生物技术
·
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jialu Gao,Hua Zhu,Huanhuan Cai,Qihang Ding,Xiaoxing Xiong,Tong Zhang,Bo Chen,Wumei Wang,Xinpeng Ju,Jianying Huang,Xiaodong Zeng,Jong Seung Kim,Xuechuan Hong
Reducing foam cell formation and accumulation within plaques is a critical strategy for treating atherosclerosis. Although current lipid-lowering therapies have significantly improved the management of atherosclerosis, the risk of cardiovascular events remains. Thus, it is necessary to explore next-generation therapies to reduce foam cell formation, inflammation, and oxidative stress. To address these challenges, we present an innovative near-infrared II (NIR-II) fluorescent dye coupled with a lesion-targeting peptide, forming a molecular self-assembly nanoplatform for effective in vitro small interfering RNA (siRNA) delivery. This platform downregulates Epsin1/2, a family of ubiquitin-binding endocytic adaptors, upregulates the expressions of ABCG1 and LRP-1 proteins, and markedly reduces foam cell formation. Additionally, this system enables real-time tracking of plaque accumulation, therapeutic response, and efficacy through in vivo noninvasive NIR-II imaging. Systemic siRNA delivery significantly suppresses lipid accumulation, plaque size, and necrotic core area in the carotid plaque model of ApoE −/− mice. These results suggest that this multi-functional nanoplatform could become an effective tool for NIR-II image-guided siRNA delivery for personalized treatment of atherosclerosis.
研究领域:
医学
·
生物技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
STAR Protocols
·
2021
·
IF 0
Lidia Wrobel,Farah H. Siddiqi,David C. Rubinsztein
Summary We present a protocol for in vivo siRNA-mediated knockdown of a gene of interest in mouse liver using systemic delivery via intravenous injection. We describe a step-by-step protocol for delivery of siRNA particles, with tips on how to optimize dosage. We detail steps for feeding/starving cycles as well as for liver tissue isolation, followed by gene expression analysis, measured at the mRNA and protein levels. For complete information on the generation and use of this protocol, please refer to Wrobel et al. (2020) .
研究领域:
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
MOLECULES
·
2021
·Vol. 26
·期 11
·3238
·
IF 4.412
Shuang Liu,Shaohui Deng,Xiaoxia Li,Du Cheng
Though siRNA-based therapy has achieved great progress, efficient siRNA delivery remains a challenge. Here, we synthesized a copolymer PAsp(-N=C-PEG)-PCys-PAsp(DETA) consisting of a poly(aspartate) block grafted with comb-like PEG side chains via a pH-sensitive imine bond (PAsp(-N=C-PEG) block), a poly(l-cysteine) block with a thiol group (PCys block), and a cationic poly(aspartate) block grafted with diethylenetriamine (PAsp(DETA) block). The cationic polymers efficiently complexed siRNA into polyplexes, showing a sandwich-like structure with a PAsp(-N=C-PEG) out-layer, a crosslinked PCys interlayer, and a complexing core of siRNA and PAsp(DETA). Low pH-triggered breakage of pH-sensitive imine bonds caused PEG shedding. The disulfide bond-crosslinking and pH-triggered PEG shedding synergistically decreased the polyplexes’ size from 75 nm to 26 nm. To neutralize excessive positive charges and introduce the targeting ligand, the polyplexes without a PEG layer were coated with an anionic copolymer modified with the targeting ligand lauric acid. The resulting polyplexes exhibited high transfection efficiency and lysosomal escape capacity. This study provides a promising strategy to engineer the size and surface of polyplexes, allowing long blood circulation and targeted delivery of siRNA.Keywords:small polyplex;pH-sensitive PEG shedding;disulfide bond-crosslinking;siRNA delivery;targeting delivery
研究领域:
药学
·
分子生物学
·
纳米技术
✓ 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）