BIOMATERIALS
·
2018
·
IF 8.806
Baiping Mao,Caixia Liu,Wenwen Zheng,Xiaoheng Li,Renshan Ge,Haifa Shen,Xiaoling Guo,Qingquan Lian,Xian Shen,Chao Li
Regenerated silk fibroin (SF) is a natural biomacromolecule with excellent biocompatible and biodegradable properties. In this study, cyclic pentapeptide cRGDfk and Chlorin e6 (Ce6) were conjugated to SF polypeptides , and genipin was used to prepare 5-fluorouracil (5-FU) doped SF-based nanoparticles (NPs). The photodynamic therapy (PDT) potential and active targeting properties were systematically investigated in α v β 3 integrin receptor over-expressed MGC-803 cells in vitro. The results revealed that treatment with the multifunctional SF-based NPs and PDT, high level of reactive oxygen species (ROS) and cell death can be induced in MGC-803 cells. Combine with PDT, the in vivo antitumor effect of the SF-based NPs was evaluated in gastric cancer xenograft mice model. The results demonstrated that the SF-based NPs had ideal active tumor targeting property and the tumor burden can be reduced noticeably. Furthermore, the organs of mice in SF NPs treatment groups did not show obvious toxicity, demonstrating good biocompatibility and security profiles of SF NPs in vivo. Overall, our results suggest that the SF-based NPs are promising drug delivery carriers, together with PDT, the multimodality therapy could be potential regimen in future clinical cancer treatment.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2020
·Vol. 18
·期 1
·1-11
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IF 6.518
Ji De,Wang Qiaohan,Zhao Qi,Tong Huangjin,Yu Mengting,Wang Meng,Lu Tulin,Jiang Chengxi
Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin αvβ3 and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis.
研究领域:
药理学
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分子生物学
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纳米医学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2021
·Vol. 27
·期 49
·12589-12598
·
IF 5.236
Sangni Jiang,Wenliang Wang,Lihua Dong,Xinxin Yan,Shengran Li,Weikang Mei,Xintao Xie,Yuanhua Zhang,Sanrong Liu,Xifei Yu
Graphical Spot on : A light-inducible Lip-cRGDfk/ICG/Dox liposome simultaneously loads a water-soluble drug (Dox) and photothermal transduction agents (ICG), targets the tumor site, and locally heats it up under external laser irradiation. Due to the conformational transformation of CP lipids, the anticancer drug Dox is released at a specific time and in a specific space to kill tumor cells. This brings about a combination of chemotherapy and photothermal therapy for the noninvasive treatment of tumors. Choline phosphate lipids have been designed and developed as new-generation zwitterionic nanocarriers with excellent biocompatibility and bioorthogonality to provide a more programmable performance for cancer therapy. However, there is a lack of spatiotemporal and reversible control for drug release at target tumor cells, which can lead to severe adverse effects to normal tissue and discounted treatment outcome. Here, light-inducible Lip-cRGDfk/ICG/Dox liposomes were developed for synergistic cancer therapy. ICG can effectively convert light energy into selective heating in a local environment upon laser irradiation, thus inducing thermal ablation of tumor cells, and further reversibly trigger the spatiotemporal release of anticancer drugs (Dox) at tumor cells due to the conformation transformation of CP lipids to synergistically kill tumor cells. That Lip-cRGDfk/ICG/Dox exhibited a significant improvement for breast cancer therapy in vitro and in vivo is also demonstrated, thus it can serve as an efficient platform to noninvasively and spatiotemporally control the activation of cytotoxicity at tumor cells for precision cancer therapy.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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