CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Han Yang,Min Liu,Jingwen Jia,XiaoFang Li,Siyi Liu,Jingya Xiu,Jiulong Zhang,Xiuli Zhao
Rheumatoid arthritis (RA) is an auto-immune disease characterized by the excessive production of pro-inflammatory factors siRNA-mediated RNA interference offers a promising alternative owing to its high specificity and minimal side effects. However, the current cationic gene delivery system has always suffers from systematic toxicity due to excess cationic groups in the carrier. To overcome this drawback, we introduced a biomimetic siRNA delivery system with no cationic moiety, EHPS, using epigallocatechin gallate (EGCG) to condense TNF-α siRNA through hydrogen bonding, electrostatic interactions, and hydrophobic forces for the treatment of RA. Additionally, we enhanced this system with M1 macrophage membrane (M1m)-coated nanoparticles (termed M−EHPS) to evade the immune system and selectively target inflammatory cells. This design improved nanoparticle stability through additional hydrogen and hydrophobic bonding and reduced toxicity caused by conventional cationic carriers. M−EHPS could respond to high concentration of reactive oxygen species (ROS) in RA, facilitating rapid siRNA release from lysosomes via the proton sponge effect. Critically, this nanosystem also released EGCG, which mitigated a broad spectrum of reactive oxygen and nitrogen species (RONS), thereby creating a synergistic effect with siRNA. In RA mice model, intravenous administration of M−EHPS achieved targeted accumulation in inflamed joints and demonstrated potent anti-RA efficacy. This novel siRNA delivery system, integrating triple-interaction stability and intrinsic self-destructive release capability, presents a robust and efficient approach for targeted RA therapy and has significant potential for advancing RNA interference therapeutics in other diseases.
研究领域:
医学
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生物技术
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-22
·
IF 12.6
Liu Yanhong,Gong Liming,Feng Jing,Xiao Congcong,Liu Chenfei,Chen Bohan,Chen Liqing,Jin Mingji,Guan Youyan,Gao Zhonggao,Huang Wei
Immune checkpoint inhibition (ICI) has become the mainstay of immunotherapy for the treatment of renal cell carcinoma (RCC). However, only a small portion of patients exhibit a positive response to PD-1/PD-L1 blockade therapy and the key reason is that RCC belongs to a vascular-rich tumor for promoting immunosuppression. Specifically, the dysfunctional tumor vasculature hinders effector T cell infiltration and induces immunosuppressive tumor microenvironment via the release of cytokine, which attenuates the therapeutic efficacy of ICI. Therefore, regulating abnormal tumor vasculature may be a promising strategy to overcome the immunosuppressive microenvironment and enhance ICI therapy. Here, we propose an NGR peptide-modified actively targeted liposome (Axi/siRNA PD−L1 @NGR-Lipo) to encapsulate the anti-angiogenic agents Axitinib and PD-L1 siRNA to promote tumor vasculature normalization and relieve immune evasion for enhanced anti-tumor immunotherapy. With NGR-mediated tumor homing and active targeting, Axi/siRNA PD−L1 @NGR-Lipo could act on tumor vascular endothelial cells to inhibit neo-angiogenesis, increase pericyte coverage and vascular perfusion, and normalize the structure and function of tumor blood vessels. Meanwhile, it also enhanced immune effector T cells and NK cells infiltration and reduced the proportion of immunosuppressive T cells including MDSC cells and Tregs, thus improving the tumor immunosuppressive microenvironment. Moreover, Axi/siRNA PD−L1 @NGR-Lipo reduced the expression of PD-L1 protein in tumor cells, restored the recognition and killing ability of cytotoxic T cells, and relieved immune evasion. As expected, Axi/siRNA PD−L1 @NGR-Lipo displayed superior anti-tumor and anti-metastatic efficacy in mice bearing RCC. Overall, this study demonstrated the important potential of regulating abnormal tumor vasculature to reshape the immunosuppressive microenvironment and boost ICI therapy, which represents a promising avenue for the synergistic anti-tumor with cancer immunotherapy. Graphical
研究领域:
肿瘤学
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免疫学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Xiaoyan Zhou,Qianqian Zheng,Changyong Wang,Jiake Xu,Jian-Ping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.
研究领域:
药物学
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癌症研究
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聚合物化学
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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
·
2018
·
IF 8.097
Junyi Che,Yonger Xue,Jia Feng,Guang Bai,Weien Yuan
To achieve a successful delivery of siRNA by carriers in vivo, the degradation of polymers in response to tiny intracellular changes should be seriously considered. In addition, the balance between degradation and stability of polymers is another key point for high performance of carriers. In this study, imine and disulfide linkages, which are sensitive to pH changes and redox environment, respectively, were constructed as the main backbone of polymers to deliver siRNA at the intracellular and animal level. Comparisons were made between performances of these two different polymers. Both of the polymers synthesized here have good ability to condense siRNA. However, polyplexes formed by the imine backbone-based polymer (TPSP) showed a larger particle size and a higher zeta potential than that of the disulfide backbone-based polymer (DTDPS). Although both TPSP and DTDPS could deliver the target siRNA into 7721 cells, polyplexes formed by TPSP showed a higher silence efficiency in vitro and accomplished more accumulation in tumors. In conclusion, we believe TPSP is superior to be used for siRNA delivery and promises a potential for widespread use.
研究领域:
药学
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生物技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Fangdi Wei,Yuan Yao,Qiutong Chen,Jiamei Song,Zhen Xie,Li Ai,Guanhong Xu,Yao Cen,Yuhui Lin,Jing Yang,Qin Hu,Rui Li
Inspired by the distinctive merits of carbon nanoparticles (CNPs) and poly(amidoamine) (PAMAM) dendrimers, we synthesized PAMAM modified CNPs (CNPs-PAMAM). First, CNPs were prepared using citrate acid and 1, 2, 4-triaminobenzene. Then, PAMAM was anchored on the surface of CNPs. The structure of PAMAM would remain unchanged under mild conditions of the postmodification method, making PAMAM retain its excellent drug carrying ability. Particularly, CNPs-PAMAM had exceptional optical properties of excitation-independent long wavelength emission. Excitation-independent emission can ensure the sensitivity of bioimaging. Long wavelength emission can avoid the autofluorescence interference of biological matrixes and have good tissue penetration. Further studies demonstrated that CNPs-PAMAM were able to electrostatically bind and condense small interfering RNA (siRNA) into stabilized nanocomplexes. The siRNA complexed with CNPs-PAMAM was endowed with an increased resistance against degradation and an enhanced cellular uptake. Moreover, CNPs-PAMAM-complexed siRNA targeting histone deacetylase 2 (HDAC2) could be effectively delivered into the neuron-like PC-12 cells, and exert its gene-silencing effect. Precisely inhibiting the so-called undruggable target HDAC2 opens a novel strategy for ischemic stroke treatment. Thus, CNPs-PAMAM offer a promising delivery carrier to unleash the siRNA’s therapeutic potential.
研究领域:
纳米技术
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生物医学工程
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分子生物学
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药学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Suhui Ni,Yun Liu,Yue Tang,Jing Chen,Shuhan Li,Ji Pu,Lidong Han
The effect of gene silencing by survivin siRNA (siSurvivin) on the proliferation and apoptosis of lung tumor has been attracted more interest. GABA B receptor ligand-directed nanoparticles consisting of baclofen functionalized trimethyl chitosan (Bac-TMC) as polymeric carriers, tripolyphosphate (TPP) as ionic crosslinker, and siSurvivin as therapeutic genes, were designed to enhance the survivin gene silencing. GABA B receptor agonist baclofen (Bac) was initially introduced into TMC as a novel ligand. This Bac-TMC/TPP nanoparticles increased the uptake of survivin siRNA through the interaction with GABA B receptor, further resulted in efficient cell apoptosis and gene silencing. For siRNA-loaded nanoparticles pulmonary delivery, mannitol was utilized for it delivery into pressurized metered dose inhalers (pMDI). The fine particle fractions of this formulation was (45.39 ± 2.99)% indicating the appropriate deep lung deposition. These results revealed that this pMDI formulation containing Bac-TMC/TPP nanoparticles would be a promising siRNA delivery system for lung cancer treatment.
研究领域:
药学科学
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纳米技术
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分子生物学
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药物递送系统
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yun-Chun Zhao,Li Zhang,Shi-Sen Feng,Lu Hong,Hai-Li Zheng,Li-Li Chen,Xiao-Ling Zheng,Yi-Qing Ye,Meng-Dan Zhao,Wen-Xi Wang,Cai-Hong Zheng
A novel cationic cholesterol derivative-based small interfering RNA (siRNA) interference strategy was suggested to inhibit Notch1 activation in SKOV3 cells for the gene therapy of ovarian cancer. The cationic cholesterol derivative, N-(cholesterylhemisuccinoyl-amino-3-propyl)-N, N-dimethylamine (DMAPA-chems) liposome, was incubated with siRNA at different nitrogen-to-phosphate ratios to form stabilized, near-spherical siRNA/DMAPA-chems nanoparticles with sizes of 100–200 nm and zeta potentials of 40–50 mV. The siRNA/DMAPA-chems nanoparticles protected siRNA from nuclease degradation in 25% fetal bovine serum. The nanoparticles exhibited high cell uptake and Notch1 gene knockdown efficiency in SKOV3 cells at an nitrogen-to-phosphate ratio of 100 and an siRNA concentration of 50 nM. They also inhibited the growth and promoted the apoptosis of SKOV3 cells. These results may provide the potential for using cationic cholesterol derivatives as efficient nonviral siRNA carriers for the suppression of Notch1 activation in ovarian cancer cells.
研究领域:
癌症生物学
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基因治疗
·
药学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Zixu Liu,Linxuan Zhao,Yupeng Feng,Qingqing Wang,Nan Dong,Yu Zhang,Tian Yin,Haibing He,Xing Tang,Jingxin Gou,Li Yang
Cancer vaccine-based immunotherapy has great potential; however, vaccine has been hindered by the immunosuppressive tumor microenvironment (TME). In this study, dual-responsive PEG-lipid polyester nanoparticles (PEG BR647-NP) for tumor-targeted delivery were proposed. PEG BR647-NP containing model tumor associated antigen (TAA) OVA and signal transduction and activator of transcription 3 (STAT3) siRNA were delivered to tumor. PEG BR647-NP was internalized by tumor associated dendritic cells (TADCs), where TAA and siRNA were released into cytoplasm via endo/lysosome escape effect. The released OVA was presented by the major histocompatibility complex class I to activate T cells, the released STAT3 siRNA acted to relieve TADCs dysfunction, promote TADCs maturation, improve antigen-presenting ability, and enhance anticancer T cell immunity. Meanwhile, PEG BR647-NP was ingested by tumor cells, and could kill tumor cells by the pro-apoptosis effect of STAT3 siRNA. Moreover, PEG BR647-NP could reduce the proportion of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumors and abrogate immunosuppression. The integration of relieved TADCs dysfunction, promoted TADCs maturation, enhanced antigen cross-presentation, abrogated immunosuppression, and improved pro-apoptosis effect can boost the vaccination for tumor immunotherapy. Thus, PEG BR647-NP efficiently delivered vaccine and STAT3 siRNA to tumor, and modulated immunosuppressive TME, provided better antitumor effects.
研究领域:
癌症免疫疗法
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纳米技术
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-14
·
IF 10.435
Yang Yuming,Han Yu,Sun Qiuyang,Cheng Jin,Yue Caixia,Liu Yanlei,Song Jie,Jin Weilin,Ding Xianting,de la Fuente Jesús M.,Ni Jian,Wang Xiaoqiang,Cui Daxiang
Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.Conclusion sThe development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
研究领域:
纳米技术
·
肿瘤学
·
药学
·
分子医学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Materials Interfaces
·
2017
·Vol. 4
·期 24
·1701166
·
IF 4.279
Qianyu Zhang,Li Wang,Yajun Jiang,Wei Gao,Yinsong Wang,Xiaoying Yang,Xinlin Yang,Zunfeng Liu
The multifunctional nanocomposites with grafting polyamidoamine dendrimers up to third generation (G 3 ) are grown onto the surface of mesoporous silica-coated gold nanorods (AuNRs@SiO 2 ) via a divergent technique. The resultant AuNRs@SiO 2 -G 3 nanocomposites with uniform size and excellent stability not only enable their utilization as targeted contrast agents for photothermal cancer therapy but also serve as scaffolds for the intracellular delivery of anticancer drug and small interfering RNA (siRNA) to enhance the efficiency of cancer therapy. The controlled doxorubicin (DOX) release from AuNRs@SiO 2 -G 3 nanocomposites is significantly improved under lower pH condition and near-infrared laser irradiation. The Bcl-2-targeted siRNA is transfected into tumor cells and induces knockdown of the protein expression, which is confirmed by western blot assays. Furthermore, the complementary effect of chemo- and gene therapy to MCF-7 cells for improved photothermal therapy is demonstrated by MTT assay. The DOX and siRNA coloaded AuNRs@SiO 2 -G 3 nanocomposites show much lower cytotoxicity compared to the DOX, resulting in low toxicity to normal tissues. The multifunctional nanocomposites have potential application as nanoplatforms to integrate the photothermal-chemo-gene tumor therapy with high efficiency.
研究领域:
纳米医学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Xin Jiang,Ziqing Yuan,Tingbo Ding,Ker Yu,Jibin Dong
The massive infiltration of suppressor immune cells within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is a major cause of treatment resistance. Reducing this infiltration may represent a potentially effective therapeutic strategy. Sphingomyelin synthase 2 (SMS2) is a crucial enzyme for sphingomyelin synthesis, contributing significantly to the integrity and function of the plasma membrane. In this study, we developed a self-assembling SMS2 siRNA gene expression plasmid for in vivo delivery. The SMS2 siRNA specifically inhibits SMS2 expression while preserving the expression and activity of SMS1. Administration of the self-assembling SMS2 siRNA suppresses tumor growth in a murine model of Panc02 pancreatic carcinoma, modulates the polarization of tumor-associated macrophages (TAMs), and reduces the infiltration of tumor-associated neutrophils (TANs) by regulating the NF-κB/CXCL5 pathway. Consequently, utilizing SMS2 siRNA to improve the local immunosuppressive microenvironment holds promise for pancreatic cancer therapy.
研究领域:
癌症生物学
·
分子生物学
·
免疫学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Suifei Li,Junyang Zhong,Yunxiao Ma,Chengfeng Yue,Wenxia Lv,Guodong Ye,Xiumei Tian,Xin Li,Yugang Huang,Lingran Du
Transcriptional gene silencing (TGS) mediated by siRNA holds promise for long-term silencing efficacy, determined by effective nuclear delivery of siRNA. However, non-viral vectors for this purpose are limited. In this work, we synthesized guanidinylated linear synthetic polypeptides (GLSPs) to explore how chain length and conformation impact siRNA delivery, especially nuclear entry. Results show that helical conformations, particularly right-handed ones, enhance siRNA loading and silencing efficiency compared to unordered structures. Increasing chain length also improves these aspects. The endocytic pathways of carrier/siRNA nanocomplexes (NCs) are mainly determined by conformation, regardless of length. Notably, some NCs derived from right-handed helices can enter cells via direct membrane penetration, like bioactivity of cell penetrating peptides (CPPs). When the peptide chain of GLSPs is long enough, all vectors can rapidly deliver siRNA to the nucleus, similar to bioactivity of nuclear localization signal peptides (NLSPs). Interestingly, helicity of the vectors aids endosomal escape of NCs. Moreover, delivering siRNA to the nucleus via GLSPs induces TGS associated with DNA promoter methylation or histone deacetylation. This study clarifies the structure-activity relationship of GLSPs in siRNA delivery, providing new insights for designing non-viral carriers for TGS.
研究领域:
分子生物学
·
基因治疗
·
药物递送系统
✓ 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）