CARBOHYDRATE POLYMERS
·
2014
·
IF 3.916
Jingfen Han,Jia Cai,Wuyinga Borjihan,Tsogzolmaa Ganbold,Tariq M. Rana,Huricha Baigude
RNA interference (RNAi) down-regulates gene expression post-transcriptionally, which is a therapeutically significant phenomenon that could potentially reduce the level of disease related proteins that are undruggable by conventional small molecular approaches. However, clinical application of small interference RNAs (siRNAs) requires design of potent siRNA sequences and development of safe and efficient delivery systems. To create a biocompatible siRNA delivery agent, we chemically modified natural polysaccharide curdlan in a regioselective manner to introduce amino group in the glucose units. The resulting 6-amino-curdlan (6AC) is water soluble and forms nanoparticles upon complexing with siRNAs. The novel curdlan-based nanoparticles efficiently delivered siRNAs to human cancer cells and mouse primary cells, and reduced 70–90% of target mRNA level. Moreover, 6AC nanoparticles delivered siRNA targeting eGFP to mouse embryonic stem (mES) cells stably expressing eGFP, and produced substantial reductions of GFP protein level. The novel curdlan-based nanoparticle is a promising vehicle for delivery of short RNAs to knock down endogenous mRNAs.
研究领域:
生物技术
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分子生物学
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药物递送
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Fan Wu,Yu Qian,Chenglong Ge,Yang Zhou,Jing Yan,Xudong Li,Xun Liu,Yuheng Lei,Ziyin Zhao,Yuansong Wei,Junliang Zhu,Lichen Yin,Shanzhou Duan
The anti-tumor efficacy of radiotherapy (RT) is limited by the hypoxic and immunosuppressive tumor microenvironment (TME), which leads to RT resistance and failure in eradicating distant metastatic lesions. Herein, we developed a fluorinated nanosensitizer that could deliver both oxygen (O 2 ) and ADAR1 siRNA into tumor cells to reinforce RT by alleviating hypoxia and immunosuppression. Fluorinated poly(β-amino ester) (fPBAE) was designed to complex ADAR1 siRNA (siADAR1) via electrostatic attraction and load O 2 due to the O 2 -dissolving capacity of fluoroalkyls. The formed nanocomplexes (NCs) facilitated robust cytosolic delivery into cancer cells after intratumoral injection, enabling efficient ADAR1 silencing to promote IFN-β release and enhance DC maturation and T cell infiltration. At the meantime, O 2 was released to alleviate tumoral hypoxia. As thus, NCs significantly enhanced the anti-tumor efficacy of RT and when further coupled with programmed death ligand-1 antibody, they effectively restrained the growth of both treated primary tumors and untreated distant tumors by eliciting robust systemic immune response. This study therefore reports an enlightened strategy for remodeling the immunosuppressive TME and sensitizing radio-immunotherapy. Statement of significance The hypoxic and immunosuppressive tumor microenvironment (TME) greatly limits the anti-tumor efficacy of radiotherapy (RT). To address this critical issue, a nano-sensitizer based on fluorinated poly(β-amino ester) (fPBAE) is herein developed to mediate efficient co-delivery of oxygen (O₂) and ADAR1 siRNA into tumor cells. ADAR1 silencing promotes DC maturation and T cell infiltration to reverse immunosuppression while the released O₂ sensitizes RT. Thus, the nano-sensitizer remarkably enhances the anti-tumor efficacy of RT and elicits robust systemic immune response to eradicate primary and distant tumors when further coupled with PD-L1 antibody.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Myagmarsuren Baldan,Shuang Zhang,Qi Sun,Yan Su,Dong Mei,Ran Sun,Ao Zheng,Danni Liu,Jie Zhang,Ran Huo,Yang Tian,Le Han,Shibo Wang,Yaoqi Wang,Chunying Cui
Background Resistance to traditional treatments has spurred research into innovative therapeutic approaches for tumors. Among these innovative treatments, photothermal therapy (PTT) has gained increasing attention for its use of photothermal agents (PTAs) to convert light into heat for localized tumor ablation. However, PTT faces limitations due to heat shock protein 70 (HSP70)-mediated resistance in tumor cells. Combining PTT via indocyanine green (ICG) with siRNA HSP70 could reduce the thermal resistance of the tumor, thereby enhancing treatment efficacy. Albumin-based nanoparticles (NPs) can effectively deliver ICG and siRNA into tumor cells. When exposed to near-infrared (NIR) light, these nanoparticles trigger lysosomal escape and release, further enhancing gene silencing activity.Methods This study aimed to develop a biocompatible delivery system, HSA@ICG/siRNA NPs, for photothermal-enhanced tumor therapy. The nanoparticles were characterized for size, charge, surface functionalization, and photoconversion properties. In vitro antitumor efficacy was evaluated using MTT assay, calcein AM/PI staining, RT-PCR, and Western blot in 4T1 tumor cells. In vivo, we assessed photothermal effects, biodistribution, tumor inhibition, and biosafety following irradiation.Results Characterization confirmed the successful synthesis of uniform, stable HSA@ICG/siRNA NPs with effective photothermal conversion properties. Cellular uptake studies revealed high siRNA internalization, with laser-induced lysosomal escape enhancing cytoplasmic delivery. In vitro, gene silencing reduced mRNA and protein levels by 82.8% and 65%, respectively. In vivo, local tumor temperature increased to 42°C within 3 minutes, indicating a mild but effective photothermal effect. Tumor inhibition rates were 50.00% ± 9.16% for HSA@ICG and 71.26% ± 7.92% for HSA@ICG/siRNA, demonstrating enhanced tumor suppression. The treatment achieved sustained tumor targeting with minimal off-target toxicity.Conclusion As a dual-function photothermal therapy agent, HSA@ICG/siRNA NPs combine targeted gene silencing with photothermal effects, demonstrating significant therapeutic promise. This integrated approach addresses tumor resistance, offering a potential advancement in cancer treatment strategies.
研究领域:
生物医学工程
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肿瘤学
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基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
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IF 7.504
Xiaojun Cai,Haofang Zhu,Yanmei Zhang,Zhongwei Gu
RNA interference (RNAi) has a great promise in treating various acquired and hereditary diseases. However, it remains highly desirable to develop new delivery system to circumvent complex extra- and intracellular barriers for successful clinical translation. Here, we report on a versatile polymeric vector, bioreducible fluorinated peptide dendrimers (BFPD), for efficient and safe small interfering RNA (siRNA) delivery. In virtue of skillfully integrating all of the unique advantages of reversible cross-linking, fluorination, and peptide dendrimers, this novel vector can surmount almost all extra- and intracellular barriers associated with local siRNA delivery through highly improved physiological stability and serum resistance, significantly increased intratumoral enrichment, cellular internalization, successful facilitation of endosomal escape, and cytosolic siRNA release. BFPD polyplexes, carrying small interfering vascular endothelial growth factor (siVEGF), demonstrated excellent VEGF silencing efficacy (∼65%) and a strong capability for inhibiting HeLa cell proliferation. More importantly, these polyplexes showed superior performance in long-term enrichment in the tumor sites and had a high level of tumor growth inhibition. Furthermore, these polyplexes not only exhibited excellent in vivo antitumor efficacy but also demonstrated superior biocompatibility, compared with LPF2000, both in vivo and in vitro. These findings indicate that BFPD is an efficient and safe siRNA delivery system and has remarkable potential for RNAi-based cancer treatment.
研究领域:
药剂学
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分子生物学
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癌症研究
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2014
·Vol. 12
·期 1
·1-12
·
IF 4.078
Wang Qing,Zhang Chunlei,Shen Guangxia,Liu Huiyang,Fu Hualin,Cui Daxiang
Background Fluorescent carbon dots (Cdots) have attracted increasing attention due to their potential applications in sensing, catalysis, and biomedicine. Currently, intensive research has been concentrated on the synthesis and imaging-guided therapy of these benign photoluminescent materials. Meanwhile, Cdots have been explored as nonviral vector for nucleic acid or drug delivery by chemical modification on purpose.Results We have developed a microwave assisted one-step synthesis of Cdots with citric acid as carbon source and tryptophan (Trp) as both nitrogen source and passivation agent. The Cdots with uniform size show superior water solubility, excellent biocompatibility, and high quantum yield. Afterwards, the PEI (polyethylenimine)-adsorbed Cdots nanoparticles (Cdots@PEI) were applied to deliver Survivin siRNA into human gastric cancer cell line MGC-803. The results have confirmed the nanocarrier exhibited excellent biocompatibility and a significant increase in cellular delivery of siRNA, inducing efficient knockdown for Survivin protein to 6.1%. In addition, PEI@Cdots complexes mediated Survivin silencing, the arrested cell cycle progression in G1 phase as well as cell apoptosis was observed.Conclusion The Cdots-based and PEI-adsorbed complexes both as imaging agents and siRNA nanocarriers have been developed for Survivin siRNA delivery. And the results indicate that Cdots-based nanocarriers could be utilized in a broad range of siRNA delivery systems for cancer therapy.
研究领域:
纳米技术
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生物医学
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癌症治疗
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 11
·3075-3084
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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
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药学科学
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Xiaolei Ma,Rui Cong,Xin Cui,Yiwei Tang,Jie Ren,Jinfan Hou,Boyu Liu,Jiehui Zhao,Pengwei Li,Lei Li,Heyang Zhang,Jiasheng Tu,Lei Jiang
Psoriasis is a prevalent chronic inflammatory skin disease characterized by immune cell activation and aberrant keratinocyte proliferation. Signal transducer and activator of transcription 3 (STAT3) plays a key role in the pathology of psoriasis, positioning it as a promising target for therapeutic strategies. However, current STAT3 inhibitors often lack specificity, leading to adverse effects. Here, we present the development of dendritic lipopeptides (DLPs) designed to facilitate the transdermal delivery of small interfering RNA (siRNA) to specifically inhibit STAT3 expression in psoriatic lesions. The dendritic architecture and peptide composition of DLP are crucial for interaction with keratin of stratum corneum and gene transfection efficiency, while the lipid chain selection aims to increase lipophilicity and enhance interactions with cellular membranes. We conducted extensive in vitro and in vivo investigations to assess the therapeutic efficacy of these DLPs for siRNA delivery in psoriasis treatment. The results demonstrated that our DLPs effectively penetrated the skin barrier, delivered siRNA to target cells, and significantly reduced STAT3 expression, regulated immune cell imbalance, leading to a marked improvement in psoriasis symptoms. In conclusion, our study presents a promising non-invasive approach to psoriasis treatment by focusing on the targeted suppression of STAT3 expression. The dendritic lipopeptides offer a safe and effective platform of siRNA delivery, potentially revolutionizing the management of psoriasis and other chronic inflammatory dermatological conditions.
研究领域:
皮肤病学
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分子生物学
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药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yamei Gao,Chao Chen,Chunyu Cao,Xueting Shen,Silin Shi,Shiyu Du,Donghong Sun,Jiliang Lu,Xiaozheng Jiang,Xin Han,Zhiqiang Yin
Psoriasis is a chronic inflammatory dermatosis with excessive activation of toll-like receptors (TLRs). Small interfering RNA (siRNA) has been considered a promising therapeutic approach by significantly suppressing mRNA expression. However, the low skin barrier penetration and the poor stability of siRNA pose a key challenge. Herein, we developed a novel and near-infrared (NIR) activated nanosystem (termed as GD-siMYD88@SPN/DA) that utilizes the gold nanorod (GNR) with highly photothermal conversion efficiency to realize localized thermal effects and photothermal-controlled release of siMYD88. Meanwhile, the shell grafted desmosome core-glycoprotein3 (Dsg3) antibody endowed it with the ability to target keratinocytes. The endocytosis of GD-siMYD88@SPN/DA by HaCaTs was significantly higher than that of the non-targeted nanosystem (GD-siMYD88@SPN), and the GD-siMYD88@SPN/DA exhibited enhanced stability in the skin. The double strand formed by the GNR-linked DNA fragment and siMYD88 serves as controlled element in response to photothermal stimulation, achieving controlled release of siMYD88. Knockdown of the MYD88 gene could effectively inhibit the TLR/MYD88/NF-κB signaling pathway, thereby reducing the production of psoriasis-related inflammatory factors. Notably, the synergistic therapeutic effects of mild-photothermal therapy combined with GD-siMYD88@SPN/DA were observed both in vitro and in vivo . Overall, this spatiotemporally controllable approach provides a versatile strategy for controllable gene therapy and mild-photothermal therapy for psoriasis.
研究领域:
皮肤病学
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分子生物学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2013
·
IF 1.7
Yiyi Wang,Peifeng Liu,Jing Du,Ying Sun,Fenghua Li,Yourong Duan
This study aims to determine the specificity of anti-human epidermal growth factor receptor antibody (anti-HER2) modified monomethoxy polyethylene glycol-chitosan (mPEG-CS) nanoparticles (anti-HER2/mPEG-CS NPs) in delivering small interfering RNA (siRNA) to the human epidermal growth factor receptor 2 (HER2) positive cancer cells. Physicochemical properties of the siRNA-loaded anti-HER2/mPEG-CS NPs (anti-HER2/mPEG-CS-siRNA NPs), including size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by particle size and zeta potential analyzer, and ultraviolet–visible spectrophotometer. MTT assay was used to study the in vitro cytotoxicity of the NPs. Fluorescent microscope and flow cytometer analysis results showed that anti-HER2/mPEG-CS-siRNA NPs had much efficient delivery of siRNA than the siRNA alone, Lipofectamine-siRNA complexes and mPEG-CS-siRNA NPs. These results demonstrated that anti-HER2/mPEG-CS-siRNA NPs had great potential applications as a targeted strategy for siRNA delivery.
研究领域:
生物医学工程
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分子生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2021
·Vol. 13
·期 17
·2929
·
IF 4.329
Jing Miao,Liwen Zhang,Peng Gao,Huawei Zhao,Xianji Xie,Junyan Wang
Glucose Transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors, which is an important factor in radioresistance of laryngocarcinoma. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngocarcinoma. GLUT-1 siRNA was designed to inhibit the GLUT-1 expression, but the high molecular weight and difficult drug delivery limited the application. Herein, we constructed a glycolipid polymer chitosan oligosaccharide grafted stearic acid (CSSA) to conjugate siRNA via electrostatic interaction. The characteristics of CSSA and CSSA/siRNA were studied, as well as the radiosensitization effect of siRNA on human laryngocarcinoma epithelial (Hep-2) cells. Compared with the traditional commercial vector LipofectamineTM2000 (Lipo), CSSA exhibited lower cytotoxicity, more efficiently cellular uptake. Incubating with CSSA/siRNA, the survival rates of Hep-2 cells were significantly decreased comparing with either the group before transfection or Lipo/siRNA. CSSA is a promising carrier for efficient siRNA delivery and radiosensitization of laryngocarcinoma.Keywords:GLUT-1;siRNA;chitosan oligosaccharide grafted stearic acid;laryngocarcinoma;radiosensitization
研究领域:
癌症生物学
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药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Jing-E Zhou,Lei Sun,Li Liu,Yujie Jia,Yuqiao Han,Jiaqi Shao,Jing Wang,Yiting Wang,Lei Yu,Zhiqiang Yan
HMGB1 is an inflammatory factor produced by macrophages after liver injury, which plays a key role in promoting NASH progression and further developing into liver fibrosis and cirrhosis. In this study, a mannose-modified HMGB1-siRNA loaded stable nucleic acid lipid particle delivery system (mLNP-siHMGB1) was constructed to target liver macrophages with mannose receptor mediation, thereby silencing HMGB1 protein expression and treating NASH. We also examined the effect of co-administration with docosahexaenoic acid (DHA), a kind of unsaturated fatty acid , on NASH. The results showed that mLNP-siHMGB1 could target macrophages through mannose receptors, effectively silence HMGB1 gene, reduce the release of HMGB1 protein in the liver, regulate liver macrophages to be an anti-inflammatory M2 phenotype, effectively reduce hepatic lobular inflammation and bullous steatosis in the liver, and restore the liver function of NASH model mice to a normal level. After 8 weeks of combined treatment with mLNP-siHMGB1 and DHA, the liver function of NASH model mice recovered rapidly and the hepatic steatosis returned to normal level. In view of inflammation, a key factor in the progression of NASH, we provided an actively targeted siRNA delivery system in this study, and clarified the important role of the delivery system in phenotypic regulation of liver macrophages in NASH. In addition, we also demonstrated the effectiveness of DHA co-administration in NASH treatment. This study provided a useful idea and scientific basis for the development of therapeutic strategies for NASH in the future.
研究领域:
药理学
·
分子生物学
·
治疗学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
危险品化学品经营许可证（带存储）