Bioactive Materials
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2021
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IF 14.593
Jiaxin Chen,Haifeng Zhu,Yutao Zhu,Chenchen Zhao,Shengyu Wang,Yixin Zheng,Ziang Xie,Yang Jin,Honghai Song,Linjun Yang,Jin Zhang,Jiayong Dai,Zhijun Hu,Huaiyu Wang
Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING–NF–κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc (IVD) degeneration. Herein, we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid (HA-CHO) and poly(amidoamine) PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment, where the formation of dynamic Schiff base bonds in the system ( [email protected] gel ) was able to overcome the shortcomings such as low cellular uptake, short half-life, and rapid degradation of siRNA-based strategy. PAMAM not only formed complexes with siRNA to promote siRNA transfection, but also served as dynamic crosslinker to construct hydrogel, and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells. Finally, the [email protected] gel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model, revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2020
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IF 8.758
Tingjie Yin,Yanqi Liu,Mengnan Yang,Lei Wang,Jianping Zhou,Meirong Huo
Despite the great potential of combination therapy based on siRNA and chemotherapeutics, an efficient vehicle with abilities of well drug co-loading, synchronizing in vivo trafficking, and target-specific co-burst release remains elusive, which results in a suboptimal synergistic potency. Herein, a novel chitosan amphiphile (PEI-ss-HECS-ss-OA, HSPO) with glutathione (GSH)-reversible cationization and hydrophobicization by polyethylenimine (PEI) and octylamine (OA), respectively, was developed for this purpose. HSPO spontaneously assembled in aqueous solution to be a micellar system and effectively co-encapsulated the two drugs with an adjustable dosage ratio. With a surface charge inversion strategy by hyaluronic acid (HA) coating, the HA(HSPO) co-delivery micelles with a negative surface charge (−21.45 ± 1.44 mV) and suitable size (192.52 ± 7.41 nm) selectively accumulated into CD44 overexpressed A549 tumors through a combination of passive and active targeting mechanism. Then, tumor cytoplasm-selective co-burst release was obtained through GSH triggered collapse of the amphiphilic assembly alongside a decrease of positive charge condensation, finally leading to an enhanced synergistic antitumor effect with a superior inhibition ratio of 86.63%. Overall, this study validated the great promise of HSPO as an efficient site-specific rapid co-trafficking vehicle of siRNA and chemotherapeutics for a remarkable synergistic tumor inhibition.
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高影响因子
Acta Biomaterialia
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2021
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IF 8.947
Ye Yuan,Jia Liu,Xiangnan Yu,Xingxin Liu,Yanni Cheng,Cheng Zhou,Mingyi Li,Lin Shi,Yan Deng,Huan Liu,Guobin Wang,Lin Wang,Zheng Wang
Multidrug resistance (MDR) is a major cause accounting for chemotherapy failure and recurrence of malignant tumors. A prominent mechanism underlying MDR is overexpression of P-glycoprotein (P-gp, a drug efflux pump). Promoting drug delivery efficacy by targeting tumor and concurrently suppressing drug efflux through down-regulating P-gp emerges as an effective strategy to enhance intracellular drug accumulation for combating MDR tumor. General Control Non-repressed 5 (GCN5), a histone acetyltransferase acting as an epigenetic regulator of multidrug resistance protein 1 (MDR1), positively regulates P-gp levels in drug-resistant cancer cells. Herein, a hyaluronic acid-coated, pH/redox dual-responsive nanosystem (HPMSNs) is fabricated for co-delivering doxorubicin (DOX) and GCN5 siRNA (siGCN5). This nanosystem can effectively encapsulate DOX and siRNA preventing premature leakage and releasing these therapeutics intracellularly via its pH/redox dual responsiveness. Through CD44-mediated targeting, DOX/ [email protected] increases drug internalization in CD44-overexpressing cancer cells, and markedly promotes DOX retention by down-regulating P-gp expression in drug-resistant cancers through silencing GCN5. Of note, in an MDR breast tumor model, DOX and siGCN5 co-delivered HPMSNs inhibits MDR tumor growth by 77%, abolishes P-gp-mediated drug resistance, and eliminates DOX's systemic toxicity. Thus, the tumor-targeting, stimuli-responsive nanosystem is an effective carrier for co-delivering anticancer drug and siRNA for combating cancer drug resistance. Statement of significance We designed a tumor-targeting, pH/redox dual-responsive nanosystem (HPMSNs) for chemo-drug and siRNA co-delivery. This nanosystem efficiently co-delivered DOX and siGCN5 into drug-resistant cancer cells and significantly inhibited the tumor growth through: (1) HA shell enhanced the cellular internalization of loaded DOX and siGCN5 via CD44-mediated targeting; (2) the pH/redox dual-responsive nanosystem released the cargos in response to the intracellular environment; (3) the released siGCN5 downregulated P-gp epigenetically. In an MDR breast tumor model (MCF7/ADR), DOX and siGCN5 loaded HPMSNs markedly inhibited tumor growth, almost completely abolished P-gp expression, and minimized systemic toxicity of DOX.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Guirong Zheng,Yiling Shen,Ruirui Zhao,Fan Chen,Ying Zhang,Aixiao Xu,Jingwei Shao
A targeting drug delivery system (TDDS) can selectively deliver antitumor drugs to cancerous parts to improve its anticancer efficacy. Hence, a targeted drug delivery system (UA/siVEGF@MSN-FA) coloading ursolic acid (UA) and vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) based on mesoporous silica (MSN) nanocarrier modified by a folic acid (FA) molecule was designed and synthesized. The MSN-FA nanoparticles were investigated for shape, diameter, and zeta potential and and by infrared (IR) spectroscopy. FR-overexpressing HeLa cells and FR-negative HepG2 cell lines were used to evaluate the in vitro cellular uptake and the cytotoxicity of MSN-FA nanoparticles. The morphology of HeLa cells transfected with siVEGF@MSN-FA was observed using fluorescence microscopy. Our findings demonstrated that UA@MSN-FA nanoparticles were near-spherical, and the particle size was about 209 ± 9.21 nm. The MSN-FA nanocarrier not only could enhance the in vitro transfection efficiency and the stability of siVEGF but also could further improve the targeted anticancer efficacy of UA and siVEGF via the active targeting property of FA. Overall, the MSN-FA drug delivery system could serve as an excellent material in biomedical applications.
研究领域:
药理学
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纳米技术
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癌症研究
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分子生物学
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高影响因子
PROCESS BIOCHEMISTRY
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2022
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IF 4.885
Shiying Zeng,Qinglai Tang,Kang Jiang,Xiaojun Tang
Metformin (MET) and survivin siRNA were delivered using silk fibroin nanoparticles (SFNs) modified with polyethyleneimine (PEI). Nanoparticle functional groups, structural, stability and physicochemical characteristics of the nanoparticles were determined. SFNs loaded with siRNA that had appropriate size, zeta potential , and stability were confirmed by various analytical and spectroscopical methods. The vitro cytotoxicity analysis was performed using CNE2 nasopharyngeal carcinoma cells with different compositions, and the results showed that the newly fabricated nanoparticles effectively triggered apoptosis in CNE2. Afterward, the mice analysis was used to investigate the in vivo therapeutic efficacy. With no apparent weight loss, the co-delivery systems dramatically slowed nasopharyngeal tumor development in mice. Survivin siRNA and MET increased the number of apoptotic tumor cells on histopathology slides. Apoptosis induction in cancer cells and therapeutic effectiveness were satisfactory with the drug delivery method. In this way, it might be used as a therapeutic agent in the fight against nasopharyngeal cancer.
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高影响因子
ACS Applied Materials & Interfaces
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2022
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IF 10.383
Qing Hu,Jiayi Yao,Xiaoqin Wang,Yanfang Wang,Xiaoling Fu,Ju Ma,Han Lin,Jiaqi Xu,Longhua Shen,Xiangbin Yu
Chemoimmunotherapy can synergistically enhance the therapeutic effects and decrease the side effects by a combined method. However, the effective targeted codelivery of various chemotherapeutic agents and siRNAs remains challenging. Although nanomedicine-based chemoimmunotherapy has shown great potential in cancer treatment in recent years, further effort is needed to simplify the nanocarrier designs and maintain their effective functions. Here, we report a simple but robust multifunctional liposomal nanocarrier that contains a pH-sensitive liposome (LP) shell and a dendritic core for tumor-targeted codelivery of programmed cell death ligand 1 (PD-L1) siRNA and doxorubicin (DOX) (siPD-L1@PM/DOX/LPs). siPD-L1@PM/DOX/LPs had a suitable particle size and zeta potential, excellent stability in serum, and pH-sensitive drug release in vitro. They exhibited significant cell proliferation inhibition compared to free DOX and DOX-loaded LPs and could escape endosomes, effectively release siRNA into the cytoplasm of MCF-7 cells, and significantly reduce the PD-L1 expression on tumor cells. In vivo imaging confirmed high accumulation of siPD-L1@PM/DOX/LPs at the tumor site. More importantly, compared with siPD-L1@PM/LPs or DOX alone, siPD-L1@PM/DOX/LPs were more effective in inhibiting tumor growth and activating cytotoxic T cells in vivo. In conclusion, this nanocarrier may hold promise as a codelivery nanoplatform to improve the treatment of various solid tumors.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2023
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IF 9.9
Mengru Cai,Yu Yao,Dongge Yin,Rongyue Zhu,Tingting Fu,Jiahui Kong,Kaixin Wang,Jing Liu,Aina Yao,Yidan Ruan,Wenjuan Shi,Qian Zhu,Jian Ni,Xingbin Yin
In recent years, small interfering RNA (siRNA) has been widely used in the treatment of human diseases, especially tumors, and has shown great appeal. However, the clinical application of siRNA faces several challenges. Insufficient efficacy, poor bioavailability, poor stability, and lack of responsiveness to a single therapy are the main problems affecting tumor therapy. Here, we designed a cell-penetrating peptide (CPP)-modified metal organic framework nanoplatform (named [email protected] @survivin [email protected] , [email protected] ) for targeted co-delivery of oridonin (ORI), a natural anti-tumor active ingredient) and survivin siRNA in vivo. This can improve the stability and bioavailability of siRNA and the efficacy of siRNA monotherapy. The high drug-loading capacity and pH-sensitive properties of zeolite imidazolides endowed the [email protected] with lysosomal escape abilities. The Polyethylene glycol (PEG)-conjugated CPP (PEG-CPP33) coating significantly improved the uptake in the [email protected] in vitro and in vivo. The results showed that the co-delivery of ORI and survivin siRNA greatly enhanced the anti-tumor effect of [email protected] , demonstrating the synergistic effect between ORI and survivin siRNA. In summary, the novel targeted nanobiological platform loaded with ORI and survivin siRNA presented herein showed great advantages in cancer therapy, and provides an attractive strategy for the synergistic application of chemotherapy and gene therapy.
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高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Anna Gan,Haimiao Chen,Fei Lin,Ruixuan Wang,Bo Wu,Tingxu Yan,Ying Jia
Background Acute lung injury (ALI) is a serious respiratory ailment marked by dysregulation of the immune dysregulation and an inflammatory reaction.Currently, effective treatment options for ALI are limited. Sanzi Yangqin Decoction (SZYQ) is a traditional formula used clinically to treat respiratory diseases, although its effects on ALI have not yet been fully elucidated. Purpose This research seeks to elucidate the pharmacodynamic material basis of SZYQ within the context of lipopolysaccharide (LPS)-induced ALI, thereby establishing a robust foundation for considering SZYQ as a possible intervention for improving ALI. Methods The chemical constituents of SZYQ were identified by UHPLC-QTOF-MS. The pharmacological mechanism of SZYQ on ALI was preliminarily investigated through network pharmacology. An ALI model induced by LPS was employed to evaluate the efficacy of SZYQ via histopathological analysis and other methodologies. Transcriptomic analysis of lung tissue from ALI mice was conducted to uncover the potential mechanisms underlying SZYQ's effects. Additionally, LPS was used to induce murine alveolar macrophages (MH-S), creating an in vitro ALI model; siRNA was introduced to further validate the pharmacological mechanisms of SZYQ's protective effects on ALI. Results This study identified a total of 37 chemical components within SZYQ, and network pharmacology results indicated that these components exert their effects via the Toll-like receptor pathway. The protective effects of SZYQ on ALI are manifested by the modulation of the immune response and the reduction of lung epithelial barrier damage. Transcriptomics, western blot, flow cytometry, and siRNA experiments demonstrated that SZYQ can inhibit levels of TLR2, p-NF-κB/NF-κB, p-IκB/IκB, p-IKKα/IKKα, MyD88, NLRP3, Caspase-1 and ASC. Furthermore, SZYQ was observed to reduce the release of reactive oxygen species (ROS), suppresses inflammasome activation, as well as decrease the incidence of cell pyroptosis. Conclusions This article demonstrated for the first time that SZYQ can enhance ALI through immune regulation. The proposed mechanism of action involved the TLR2-mediated NF-κB/NLRP3 signaling pathway and the inhibition of NLRP3 inflammasome activation.
研究领域:
药理学
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免疫学
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呼吸医学
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传统中医
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高影响因子
International Journal of Nanomedicine
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2021
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IF 6.4
Jialang Zhuang,Siqi Chen,Ye Hu,Fan Yang,Qin Huo,Ni Xie
Introduction Metastatic breast cancer seriously harms women’s health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects. Methods The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds. Results The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis. Conclusion The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症治疗
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DOI
PubMed
高影响因子
World Journal of Surgical Oncology
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2026
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IF 2.8
Wang Ju,Zhang Yong,Li Heyu,Peng Jikui,Li Haijun,Gao Xiaoping
STIL is a key molecule influencing the proliferation and cell cycle of gastric cancer cells; however, STIL is also expressed in normal tissues. Therefore, designing a drug delivery system that targets gastric cancer cells is crucial for STIL-targeted therapy. In this study, we constructed exosomes targeting the HER-2 receptor and loaded with siSTIL (Anti-HER-2-Exo-siSTIL), and validated the inhibitory effects of Anti-HER-2-Exo-siSTIL on gastric cancer proliferation and metastasis in vivo. Anti-HER-2-Exo-siSTIL was able to enter SGC-7901 cells and inhibit STIL expression, significantly suppressing the growth of SGC-7901 xenograft tumors. By downregulating STIL and the anti-apoptotic protein Bcl-2, and upregulating the pro-apoptotic proteins Bax, Caspase-3, and Caspase-9, Anti-HER-2-Exo-siSTIL effectively induced apoptosis in tumor cells. Furthermore, Anti-HER-2-Exo-siSTIL selectively inhibited lung metastasis of SGC-7901 cells via hematogenous dissemination. In summary, Anti-HER-2-Exo-siSTIL specifically targets and suppresses gastric cancer proliferation and lung metastasis, demonstrating its significant translational potential for gastric cancer therapy.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Junbo Jiang,Miaomiao Zhang,Yutao Zheng,Shixin Xu,Jinxin Zhang,Zhiyi Gao,Jieru Li,Bo Li,Wenting Xu,Li Xie,Wen Zhao
Dual-Crosslinking Strategy: A dual network combining genipin-mediated Schiff base dynamic bonding and Ca 2+ coordination cross-linking for mechanical reinforcement and nanoparticle anchoring. • Nucleic acid drug delivery and gene intervention: IL-11 siRNA-loaded LNPs anchored in hydrogel enable sustained release, silencing IL-11 and fibrotic genes to inhibit myofibroblast activity and remodel collagen for anti-fibrosis. • Scar-free healing promotion: SQG/si IL11 @NPs dressing reduces scar index and thickness, restores collagen I/III ratio, downregulates α-SMA and TGF-β1, enabling near scar-free skin regeneration. Hypertrophic scars often cause functional impairment and aesthetic damage, thereby affecting patients' daily life and comfort. Moreover, existing therapies have limited efficacy and are prone to recurrence. To achieve precise genetic intervention, this study constructed a time-controlled release polysaccharide hydrogel dressing for the targeted delivery of IL-11 siRNA. This dressing is based on a chitosan quaternary ammonium (QCS)/sodium alginate (SA) double-network structure hydrogel (SQG) and loaded with cationic lipid nanoparticles (si IL11 @NPs), forming an “integrated drug-loading and cross-linking” system. SQG hydrogel also shows good antibacterial activity and anti-inflammatory properties, which is helpful to establish a wound microenvironment that inhibits scar hyperplasia. It continuously releases siRNA during the mid-to-late stage of wound healing (days 5–9). Cell experiments showed that the released nanoparticles were efficiently internalized by TGF-β1-induced myofibroblasts, significantly inhibiting their migration and proliferation and downregulating the expression of IL-11 and the typical fibrotic genes COL1A1, FN1, and ACTA2. In the rabbit ear scar model, this dressing promoted wound healing, inhibited late-stage hypertrophy, reduced the scar elevation index and thickness, improved collagen alignment and the type I/III collagen ratio, and downregulated the expression of α-SMA and TGF-β1. In summary, the SQG/si IL11 @NPs hydrogel dressing shows good potential and provides a new option for inhibiting hypertrophic scar formation in wound treatment.
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高影响因子
MOLECULAR PHARMACEUTICS
·
2025
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IF 4.5
Zhen Zhang,Hongbo Wang,Zhijun Zhang,Yaoyao Zhang,Huajing Sun,Xi Chen,Jiayu Gu,Yanling Gong
Small interfering RNA (siRNA)-based therapy, which silences disease-associated genes, has emerged as a potential therapeutic strategy for various disorders, including cancer. Lipid nanoparticles (LNPs) have become a leading platform for efficient siRNA delivery. SOX9, a family member of SRY-related high-mobility-group box (SOX) transcription factors, plays an important role in the pathogenesis and progression of colorectal cancer (CRC). Here, we developed cRGDfK peptide-modificed LNPs (R-LNPs) composed of DLin-MC3-DMA, DMG-PEG, DSPC, DSPE-PEG-cRGDfK, and cholesterol for the targeted delivery of SOX9 siRNA (siSOX9) in CRC treatment. The formulation, delivery, and antitumor effect on CRC in vitro and in vivo were explored. The optimized R-LNPs exhibited favorable physicochemical properties including a uniform particle size (159.6 ± 0.93 nm), low polydispersity index (PDI = 0.207 ± 0.016), near-neutral zeta potential (2.74 ± 0.35 mV), and high encapsulated efficiency (90.71 ± 1.63%). Additionally, R-LNPs demonstrated sustained and controlled in vitro release and good serum stability. The prepared R-LNPs were efficiently uptaken by HCT-116 via clathrin, lipid rafts, and caveolae dependent endocytosis and macropinocytosis. Subsequently, R-LNPs were colocalized with lysosomes before escaping into the cytoplasm, ensuring effective siRNA release. In vivo distribution studies confirmed tumor-specific accumulation for R-LNPs in HCT-116 xenograft models. Functionally, R-LNPs loading siSOX9 inhibited the proliferation, migration, and invasion of HCT-116 cells and Caco-2 cells (P < 0.05 or 0.01) and inhibited tumor growth and proliferation in tumor-bearing mice (P < 0.05 or 0.01). The antitumor effects were attributed to the silence of SOX9, which subsequently downregulated key oncogenic mediators, including β-catenin, cyclin D1, and c-Myc (P < 0.05 or 0.01). Furthermore, R-LNPs demonstrated favorable safety in in vivo application. In conclusion, our cRGDfK-modified LNPs loading siSOX9 represent a promising targeted therapeutic strategy for CRC, offering both efficacy and biocompatibility.
研究领域:
药剂学
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肿瘤学
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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
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生物技术
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PubMed
高影响因子
危险品化学品经营许可证（带存储）