JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2015
·
IF 3.368
Wei Cui,Anhe Wang,Jie Zhao,Xiaoke Yang,Peng Cai,Junbai Li
Crosslinked albumin nanoparticles which loaded with doxorubicin (DOX) were fabricated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and biocompatible polysaccharide, alginate (ALG), using layer-by-layer technique. Albumin nanoparticles exhibited narrow size distribution and fluorescent property. The assembled core/shell structure of the nanoparticles can be internalized more easily with the cancer cells, which attributes to TRAIL binding with death receptors. TRAIL still hold bioactive properties after assembled onto the particles. In addition, after loaded into the albumin core nanoparticles, DOX (as the chemotherapeutics) display a synergistic cytotoxic effect on cytotoxicity in combination with TRAIL in vitro . The core/shell nanostructured nanoparticles realized in this study would be used as a promising candidate for novel drug carriers.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-14
·
IF 10.2
Zhao Yitong,Bo Tao,Wang Chenfei,Yao Dingjin,Pan Chaolan,Xu Weiyi,Zhou Hao,Li Ming,Zhang Si
Extensive efforts have been dedicated to enhancing the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in cancer cells for the development of effective cancer treatments. However, highly safe and efficient delivery of TRAIL gene remains a significant challenge, especially using cationic polymers. Here, a series of highly branched-linear poly(β-amino ester)s (H-LPAEs) are developed through a unique oligomer branching strategy. H-LPAEs exhibit a more uniform distribution of linear segments and branching units, leading to excellent DNA condensation and favorable physicochemical properties of H-LPAE/DNA polyplexes. In SW1353 and BMSC cells, the optimized H-LPAEs, H-LPAE B4−S5−TMPTA , achieves superior gene transfection efficiency of 58.0% and 33.4%, which were 2.5-fold and 2.0-fold higher than that of the leading commercial gene transfection reagent, Lipofectamine 3000. Excitingly, H-LPAE B4−S5−TMPTA mediated 56.7% and 28.1% cell apoptosis in HepG2 cells and HeLa cells highlighting its potential application in cancer gene therapy. In addition, locally administered H-LPAE B4−S5−TMPTA delivered TRAIL DNA to HepG2 xenograft tumors and inhibited tumor growth in vivo. This study not only proposes a novel strategy for synthesizing poly(β-amino ester)s with a unique branched-linear topology but also identifies a promising candidate for highly efficient TRAIL gene transfection.
研究领域:
癌症研究
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基因治疗
·
聚合物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Caochuan Feng,Xiaoxiong Han,Lili Chi,Jing Sun,Feirong Gong,Yaling Shen
Combination therapy of two or more drugs has gradually become of outmost importance in cancer treatment. Cabazitaxel (CTX) is a taxoid drug and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of TNF superfamily. In this study, we prepared TRAIL-modified and CTX-loaded polymer micelle (TRAIL-M-CTX). This nanoparticle was self-assembled from biodegradable amphiphilic copolymers, monomethoxyl poly(ethylene glycol)–b-poly(DL-lactide) (mPEG-PLA) and COOH-PEG-PLA, via a nanoprecipitation method and were modified with the TRAIL protein, resulting in a particle size of 39.75 ± 0.17 nm in diameter and a drug encapsulation efficiency of 95.52 ± 1.69%. The successful coupling was confirmed by 1H NMR, FTIR spectroscopy, and DLS article size measurement. Pharmacodynamic analysis in two human cancer cell lines with different TRAIL sensitivities showed that TRAIL-M-CTX has a significantly better anticancer efficacy than the individual CTX and TRAIL protein. Importantly, TRAIL-M-CTX showed synergistic effects against TRAIL-insensitive cells (MCF-7). A study of cellular uptake implied that the modified micelles were internalized into MCF-7 cells more effectively than unmodified micelles, owing to the coupled TRAIL protein. A cell cycle assay of MCF-7 cells revealed that TRAIL-M-CTX significantly increased the sub-G1 population compared with CTX or TRIAL, thus, facilitating cancer cell apoptosis. These results suggest that TRAIL-M-CTX micelles have potential as a cancer chemotherapy formulation.
研究领域:
药学
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纳米技术
·
癌症研究
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生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2013
·Vol. 1
·期 9
·1326-1332
·
IF 0
Wei Cui,Yue Cui,Jie Zhao,Junbai Li
Layer-by-layer assembled TRAIL/ALG shells have been successfully coated on the surface of highly loaded doxorubicin (DOX) calcium carbonate (CaCO3) nanoparticles as drug carriers. The assembled core/shell structure was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). They show that the assembled TRAIL/ALG coated DOX@CaCO3 nanocomposites can be internalized by cancer cells. The outer layer of the system is TRAIL which can be specifically recognized by tumors and leads to the apoptosis of tumors. The release of DOX can directly kill the cancer cells. This demonstrates that the core/shell nanocomposites of TRAIL/ALG-CaCO3 loaded with DOX have good potential applications in the treatment of cancer.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
Acta Biomaterialia
·
2022
·
IF 10.633
Xinyao Feng,Fangshen Li,Liangliang Zhang,Wenmo Liu,Xupu Wang,Rui Zhu,Zhen-An Qiao,Bin Yu,Xianghui Yu
Traditional anticancer treatments directly target tumor cells. In contrast, cancer immunotherapy fortifies host immunity. Nanoparticles that incorporate both immunomodulatory and chemotherapeutic agents regulate the tumor microenvironment by activating immune cells and enhancing antitumor immunity. Nanoparticle-based cancer immunotherapy has received considerable attention and has been extensively studied in recent years. In this study, we developed a targeted drug delivery system to enhance immunotherapeutic efficacy and overcome drug resistance by inducing tumor apoptosis and immunogenic cell death (ICD), and activating immune cells. Periodic mesoporous organosilica nanoparticles (PMOs) bore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on their surfaces, and their inner cores were loaded with doxorubicin (DOX). TRAIL enhanced the nanoparticle-targeting capacity and worked synergistically with DOX against breast cancer cells in vitro and in vivo . Furthermore, we revealed for the first time the ability of PMOs to activate dendritic cells (DCs) and elevate ICD levels of DOX in vitro , and TRAIL further enhances the immunomodulatory function of PMOs. Systemic exposure to [email protected] induced an immune response, activated DCs and CD4 + and CD8 + T cells , and significantly suppressed tumor growth in a 4T1-bearing immunocompetent mouse model. Overall, our study demonstrates that TRAIL-modified, DOX-embedded PMO nanoparticles represent a good candidate for tumor-targeted immunotherapy, which has relatively superior therapeutic efficacy and highly promising future application prospects. Statement of significance This study revealed for the first time the ability of PMOs to elevate ICD levels and activate DCs in vitro . The results explained the immunomodulatory function of PMOs and demonstrated the synergistic effects of TRAIL and DOX in triple-negative breast cancer. In addition, immunomodulatory effects of the drug delivery vectors constructed in this study were verified in vivo .
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2021
·
IF 5.157
Lei Chen,Miao Hao,Jingmin Yan,Lin Sun,Guihua Tai,Hairong Cheng,Yifa Zhou
Heat-modified citrus pectin, a water-soluble indigestible polysaccharide fiber derived from citrus fruits and modified by temperature treatment, has been reported to exhibit anticancer effects. However, the bioactive fractions and their mechanisms remain unclear. In this current study, we isolated an active compound, trans-4,5-dihydroxy-2-cyclopentene-l-one (DHCP), from heat-treated citrus pectin, and found that is induces cell death in colon cancer cells via induction of mitochondrial ROS. On the molecular level, DHCP triggers ROS production by inhibiting the activity of succinate ubiquinone reductase (SQR) in mitochondrial complex II. Furthermore, cytotoxicity, apoptotic activity, and activation of caspase cascades were determined in HCT116 and HT-29 cell-based systems, the results indicated that DHCP enhances the sensitivity of cancer cells to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), with DHCP-induced ROS accounting for the synergistic effect between DHCP and TRAIL. Furthermore, the combination of DHCP and TRAIL inhibits the growth of HCT116 and HT-29 xenografts synergistically. ROS significantly increases the expression of TRAIL death receptor 5 (DR5) via the p53 and C/EBP homologous protein pathways. Collectively, our findings indicate that DHCP has a favorable toxicity profile and is a new TRAIL sensitizer that shows promise in the development of pectin-based pharmaceuticals, nutraceuticals, and dietary agents aimed at combating human colon cancer.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 7
·1354-1360
·
IF 4.872
Yitong Wang,Mingming Wang,Hui Chen,Hongmei Liu,Qiang Zhang,Yiyun Cheng
The delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene into cancer cells is a promising strategy for cancer treatment. However, the low transfection efficacy and/or the toxicity of vectors severely hamper the translation of TRAIL gene therapy into the clinics. In this article, we employed our recently developed fluorinated dendrimer as a vector to deliver plasmid encoding TRAIL (pTRAIL) into cancer cells for cancer treatment, which holds the advantages of both excellent transfection efficacy and low toxicity. Fluorinated poly(amidoamine) dendrimer (G4-F735) represented much higher TRAIL gene transfection efficacy than a series of transfection reagents including poly(ethylene imine) (PEI), SuperFect and Lipofectamine 2000, leading to a much higher cell apoptosis efficacy. The G4-F735/pTRAIL complex, compared with PEI/pTRAIL, could more efficiently destroy three-dimensional multicellular spheroids consisting of MDA-MB-231 cells, and suppress the tumor growth in vivo. Furthermore, G4-F735 showed minimal toxicity in vitro and undetectable systemic toxicity in vivo. From this study, the fluorinated dendrimer offers a promising prospect for TRAIL gene therapy.
研究领域:
癌症治疗
·
基因递送
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Zhang Hanming,Gao Honglin,Zhang Yicong,Han Yikun,Lin Qing,Gong Tao,Sun Xun,Zhang Zhirong,Zhang Ling,Huang Shiqi
Unique physiopathological characteristics of tumor tissues impose obstacles to the sufficient penetration of traditional nanomedicines, resulting in undesirable drug delivery efficacy and therapeutic outcomes. Here, we constructed TRAIL-[ND-HCPT] GAC , a synergistic hydroxycamptothecin (HCPT) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein co-loaded disk-shaped nanocarrier with γ -glutamyl transpeptidase responsiveness. When the novel nanodisks extravasated into the tumor interstitium, the γ -glutamyl transpeptidase overexpressed on the tumor cell membranes cleaved the γ -glutamyl portions of the nanodisk surface to produce positively charged amino groups. As a result, the cationic nanodisks possessed stronger tumor infiltration ability through transcytosis than anionic nanodisks. HCPT and TRAIL exerted synergistic antitumor effects with better overall therapeutic efficacy. This TRAIL-[ND-HCPT] GAC system performed significantly better than free HCPT and remarkably prolonged the survival of breast tumor-bearing mice with no significant toxicity.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Xiaoyuan Yang,Xuelin Xia,Xiao-Xia Xia,Zhao Sun,Deyue Yan
Tumor necrosis factor-related apoptosis ligand (TRAIL) is a promising protein candidate for selective apoptosis of a variety of cancer cells. However, the short half-life and a lack of targeted delivery are major obstacles for its application in cancer therapy. Here, we propose a simple strategy to solve the targeting problem by genetically fusing an anti-HER2 affibody to the C-terminus of the TRAIL. The fusion protein TRAIL-affibody was produced as a soluble form with high yield in recombinant Escherichia coli. In vitro studies proved that the affibody domain promoted the cellular uptake of the fusion protein in the HER2 overexpressed SKOV-3 cells and improved its apoptosis-inducing ability. In addition, the fusion protein exhibited higher accumulation at the tumor site and greater antitumor effect than those of TRAIL in vivo, indicating that the affibody promoted the tumor homing of the TRAIL and then improved the therapeutic efficacy. Importantly, repeated injection of high-dose TRAIL-affibody showed no obvious toxicity in mice. These results demonstrated that the engineered TRAIL-affibody is promising to be a highly tumor-specific and targeted cancer therapeutic agent.
研究领域:
生物技术
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Yang Junfa,Liu Qingxue,Cao Shiyang,Xu Tao,Li Xiaofeng,Zhou Dandan,Pan Linxin,Li Changyao,Huang Cheng,Meng Xiaoming,Zhang Lei,Wang Xiao
During the liver fibrosis recovery stage tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can effectively induce apoptosis of activated hepatic stellate cells (HSCs). Normal hepatic stellate cells are resistant to TRAIL cytotoxicity. Therefore, enhancing the sensitivity of TRAIL-induced apoptosis of HSCs may be useful to treat hepatic fibrogenesis. Here, we demonstrated that miR-145 and TRAIL were down-regulated in both liver fibrosis tissue samples and transforming growth factor-β1 induced HSCs, concomitant with increased the expression of ZEB2. In addition, we found that mimics-mediated over-expression of miR-145 led to resistance to the ZEB2 expression and up-regulation of the TRAIL-induced apoptosis after treatment of LX-2 cells with TRAIL. Furthermore, ZEB2-siRNA transfected LX-2 cells showed the increased sensitivity to TRAIL-induced apoptosis. Whereas, opposite results were obtained in miR-145-inhibitor group or ZEB2 plasmid group. Moreover, miR-145 regulated ZEB2 gene expression by specifically interacting with the 3′-UTR of ZEB2 mRNA to inhibit the expression of ZEB2. Further studies showed that the over-expression of ZEB2 could inhibit TRAIL-induced apoptosis via inhibiting nuclear factor-κB (NF-κB) signaling pathway in LX-2 cells. Collectively, our data suggest that up-regulation of miR-145 can down-regulate ZEB2 expression, consequently promoting TRAIL-induced apoptosis in LX-2 cells through NF-κB signaling pathway, which facilitates the resolution of liver fibrosis.
研究领域:
分子生物学
·
细胞生物学
·
肝病学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Yan Zhang,Xinyi Tan,Tianyang Ren,Chao Jia,Zaixing Yang,Hong Sun
A ternary core/shell based nanoparticulate complex was designed for the sequential and site-specific drug delivery. First, bovine serum albumin nanoparticles (BSA NPs) were served as the core for loading gambogic acid (GA). Subsequently, the BSA NPs were adsorbed by polyethylenimine and then shielded with carboxymethyl chitosan-folate (CMCS-FA) as the outer shell for encapsulating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), forming the GA/TRAIL co-delivery BSA (GTB) NPs. In normal tissues, the GTB NPs were negatively charged; in acidic tumor tissues, the shielding CMCS-FA was detached, allowing the release of TRAIL, which binds to the cell death receptor on the plasma membrane. The resulting positively charged complex promoted cellular internalization and escaped from lysosomes, producing a rapid release of GA, which exerted the combined tumor therapy by regulating both intrinsic and extrinsic apoptotic pathways. In vitro and in vivo studies confirmed that GTB NPs could enhance antitumor efficacy and reduce adverse effects.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jianhao Xie,Juan Su,Wanqi Zhou,Simin Cai,Wenfeng Liao,Jianing Zong,Junfeng Peng,Huanhuan Qu,Fei He,Kan Ding
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Recent pharmacological studies suggested that Lamiophlomis rotata might contain components with antitumor activities. In this study, we aimed to investigate the potential of polysaccharides as active components in Lamiophlomis rotata . Our findings suggest that a polysaccharide, LRP01B, from Lamiophlomis rotata induces PDAC cells apoptosis by causing mitochondrial dysfunction and oxidative stress in vitro and in vivo . LRP01B is a homogeneous polysaccharide with a molecular weight of 15.9 kDa, composed of galactose, glucose, xylose, arabinose, rhamnose, and galacturonic acid in a molar ratio of 0.7: 0.3: 0.1: 1.1: 1.0: 4.3. The backbone of LRP01B mainly consists of 1,4-linked α-Gal p A, 1,2-linked α-Rha p , and 1,3-linked α-Gal p A, with existence of arabinose and xylose on the side chain. In vivo experiments demonstrate that LRP01B significantly inhibits pancreatic tumor growth in a patient-derived xenograft nude mouse model. Mechanism studies uncover that LRP01B induces apoptosis of PDAC cells through mitochondrial dysfunction and oxidative stress by recruiting TNF-related apoptosis-inducing ligand (TRAIL) to TRAIL-R1, which leads to the binding of LRP01B to both TRAIL and TRAIL-R1. Our results demonstrate that LRP01B is a dual-targeting polysaccharide with anti-PDAC activity and may be a promising anti-PDAC drug candidate.
研究领域:
癌症生物学
·
药理学
·
生物化学
·
分子生物学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
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