JOURNAL OF CONTROLLED RELEASE
·
2015
·
IF 7.705
HongYan Zhu,ShengYu Zhang,Yong Ling,GuoLiang Meng,Yu Yang,Wei Zhang
Hypoxia is a characteristic of cancer and plays a key role in tumorigenesis, angiogenesis and resistance to cancer therapies. SiRNA treatment is effective against hypoxic tumors by gene silencing. However, siRNA delivery to the hypoxic regions of solid tumors still presents a challenge due to the distance from blood vessels and the increased presence of efflux transporters. Therefore, tumor therapies would be improved through the immediate development of an effective siRNA delivery system to hypoxic regions. To this end, we synthesized a system to deliver HIF-1α siRNA into hypoxic tumor cells. The system consists of a functional shell composed of 2-deoxyglucose (DG)-polyethylene glycol (PEG) connected with the compound of lipoic acid , lysine and 9-poly- d -arginine (LA–Lys–9R) by a hydrazone bond and a core of CdTe quantum dots (QDs). The molecular structure of DG–PEG–LA–Lys–9R was confirmed by liquid chromatography–mass spectrometry (LC–MS), nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The multifunctional CdTe QDs measured approximately 200 nm and showed excellent biocompatibility , perfect siRNA binding capability and enhanced hypoxic tumor targeting. Importantly, the system described here is pH-responsive with a hydrazone bond; therefore, it avoids GLUT1 receptor-mediated endocytic recycling, resulting in irreversible delivery of the siRNA. We used Western blots to confirm the superior gene silencing efficiency induced by the DG–PEG–LA–Lys–9R with hydrazone modified CdTe QDs. Here, we demonstrate high efficacy of the siRNA tumor delivery system using in vitro and in vivo experiments. In addition, these studies demonstrate that pH-responsive hybrid quantum dots show improved antitumor efficacy with decreased organ toxicity , indicating a promising siRNA delivery system for hypoxic cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2024
·
IF 5.3
Min Fu,Yuan Li,Jingjing Liu,Junjie Liu,Jiaoxia Wei,Yuxin Qiao,Hanxin Zhong,Dongyang Han,Haitao Lu,Li Yao
Background Pulmonary hypertension (PH) is a severe cardio-pulmonary vascular disease, involves complex molecular mechanism especially during the pathological process of pulmonary vascular remodeling, brings a significant challenge to clinical treatment and thus resulting in high mortality rates. Classic Traditional Chinese medicine formula, Zhishi Xiebai Guizhi Decoction (ZXGD), holds therapeutic potential for PH. In present study, we sought to explore therapeutic potential of ZXGD against PH in rats. Methods We employed a combination methods of chemical profiling, echocardiographic, morphologic measurements, molecular biology, rats models and cultured pulmonary artery smooth muscle cells (PASMCs) to achieve this. Results Eighteen compounds were precisely identified in ZXGD using UHPLC-QTOF-MS/MS. Our data demonstrated ZXGD could alleviate PH by reducing pulmonary artery pressure and alleviating pulmonary vascular remodeling in rats. Specifically, ZXGD was found to intervene in abnormal expansion of PASMCs, thereby attenuating pulmonary vascular remodeling. ZXGD was also observed to modulate expressions of HIF-1α, ROS, and Nrf2 to alleviate hypoxia and oxidative stress. Additionally, ZXGD significantly regulated disorders in pro-inflammatory cytokines, thus mitigating inflammation. Furthermore, ZXGD decreased levels of decadienyl- l -carnitine and LDL-C, while elevating HDL-C and lipid droplet counts, thereby reducing cholesterol and lipid toxicity and preserving mitochondrial function. Importantly, inhibition of HIF-1α reversed expression of key pathological triggers for pulmonary vascular remodeling. Neohesperidin and naringin in ZXGD extract were identified as the primary contributors to its pharmacological effects against PH. Conclusion Altogether, our study empirically explored therapeutic potential and pharmacological mechanisms of ZXGD in treating PH, offering a groundwork for the development of novel anti-PH drugs. Graphical Supplementary Information The online version contains supplementary material available at 10.1186/s13020-024-01039-0.
研究领域:
药理学
·
心血管疾病
·
传统中药
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Xing Wang,Yuqi Tang,Jiankang Liang,Yongfei Zhao,Li Yang,Zhengjian Qi
TTIMN NPs prepared based on TTIMN has the function of targeting lipid droplet to induce tumor regression by depleting GSH and inactivating GPX4. Meanwhile, the mode of TTIMN NPs catalyzed the conversion of O 2 −• was also clarified according to in vivo experiments, which indicated it could initiate a series of O 2 −• -mediated bio-catalytic reactions to gain autonomously generated O 2 inside solid tumors. TTIMN NPs sensitized O 2 −• formation even under severe O 2 shortage environment, and a part of it would be converted into highly toxic OH•, subsequently triggering the release of cytochrome c and activating the cascade of the Caspase family that ultimately led to cell apoptosis. Self-generated O 2 inhibited tumor proliferation and metastasis mainly by interfering with HIF-related signaling and downregulating DNA methylation. TTIMN NPs has less systemic toxicity in blood systems and no effect on major organs, and blocked tumor progression by maintaining self-metabolism and immune system stability.
研究领域:
纳米技术
·
光动力治疗
·
肿瘤学
·
生物化学
·
药学
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Can Zhang,Shiqi Liu,Yuqing Cao,Weidong Zhang,Yuchu He,Wenkang Tu,Weili Xue,Dawei Gao,Xuwu Zhang
The hypoxic tumor microenvironment (TME) promotes tumor progression and therapeutic resistance primarily through the activation of hypoxia-inducible factor-α (HIF-α). However, current oxygen-sensitizing strategies are hindered by low delivery efficiency, transient efficacy, and severe adverse effects. In this study, we developed a composite system (C@W) comprising Chlorella pyrenoidosa (CHL) and tungsten disulfide (WS₂). This platform synergistically integrates the photosynthetic oxygen generation capacity of CHL with the photocatalytic functionality of WS₂, enabling multimodal antitumor efficacy through hypoxic TME remodeling, photocatalytic therapy, and immune activation. Upon irradiation with 660 nm near-infrared (NIR) light, CHL continuously released oxygen via in situ photosynthesis, thereby suppressing HIF-α expression and alleviating TME hypoxia. Concurrently, WS₂ efficiently catalyzed the conversion of molecular oxygen into cytotoxic singlet oxygen ( 1 O₂). Experimental results demonstrated that this system induced immunogenic cell death (ICD) in tumor cells, promoted dendritic cell maturation via damage-associated molecular pattern (DAMP) release, facilitated M2-to-M1 macrophage polarization, and significantly enhanced tumor-infiltrating CD8 + T cell populations. This bio-inorganic hybrid platform addresses the spatiotemporal limitations of conventional oxygen-enhancing therapies by establishing a dual-engine oxygen self-supply system (photosynthesis–photocatalysis). It synergistically alleviates the immunosuppressive TME while integrating microenvironment regulation with immune activation, thereby offering a novel therapeutic paradigm for solid tumor treatment.
研究领域:
肿瘤学
·
纳米医学
·
光动力治疗
·
肿瘤微环境
·
免疫治疗
·
生物杂化系统
·
光合作用生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Haitao Dou,Zixin Luo,Haodun Wang,Qicheng Duan,Zhuangzhuang Jiang,Huachao Chen,Ninghua Tan
Nanomaterial-based multi-modal synergistic therapies are emerging as highly promising strategies for the treatment of malignant tumors. Herein, a novel nanoplatform modified with the peptide of cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) was designed for synergistic treatment of hypoxic tumors by the combination of chemotherapy (CT)/photodynamic therapy (PDT)/photothermal therapy (PTT). Firstly, Mn@APDA nanoparticles were synthesized for PTT and oxygen (O 2 ) supply, consisting of an L-arginine-doped polydopamine (APDA) core and a manganese dioxide (MnO 2 ) shell. Subsequently, the liposome nanoplatform (cRGD-Lipo-MART), loaded with Mn@APDA (MA), chemotherapy drug of deoxybouvardin dodecyl ester (RA, “R” for short), and mitochondrial targeted photosensitizer of triphenylphosphine-grafted protoporphyrin IX (TPPP, “T” for short), was developed using a film dispersion method. Upon targeted delivery to tumors, the nanoplatform disintegrated in response to the acidic and hydrogen peroxide (H 2 O 2 )-rich tumor microenvironment (TME) and near-infrared (NIR) laser irradiation, thereby facilitating controlled drug release and O 2 supply to overcome hypoxia. The released RA could cause DNA damage and suppress the HIF-1α expression to sensitize PDT. Simultaneously, TPPP could generate singlet oxygen ( 1 O 2 ) and convert L-arginine (L-Arg) into nitric oxide (NO) for PDT, while APDA could induce hyperthermia for PTT. The combination of PDT and PTT resulted in significant mitochondrial dysfunction and lysosomal damage, ultimately leading to apoptosis. Furthermore, the chemotherapeutic effect of RA could be potentiated by the enhancement of cytoplasmic delivery caused by lysosomal disruption and the blocking of DNA damage repair pathway caused by mitochondrial dysfunction. Overall, cRGD-Lipo-MART, designed with a synergistic CT/PDT/PTT strategy, showed minimal systemic toxicity and could be used as an effective treatment for hypoxic tumors.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Liu Yang,Ding Lei,Chen Gaojie,Wang Peiyuan,Wang Xinghuan
Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu 2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H 2 O 2 ) catalyzed by intracellular GOx into oxygen (O 2 ), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery. Graphical Abstract
研究领域:
生物医学工程
·
纳米技术
·
癌症生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Ye Liu,Sicheng Li,Jinjian Huang,Xuanheng Li,Ze Li,Canwen Chen,Guiwen Qu,Kang Chen,Yitian Teng,Rui Ma,Xiuwen Wu,Jianan Ren
Open abdomen (OA), a major advance in modern trauma surgery, enables the treatment of severe abdominal trauma, infections, and hypertension by temporarily closing the abdominal cavity without suturing. Although OA can reduce mortality rates, it also presents challenges such as disruption of the abdominal environment, intestinal exposure, and impaired wound healing. Current temporary abdominal closure (TAC) techniques using polypropylene (PP) mesh are susceptible to abrasion and rupture of the intestine, leading to adhesions and serious complications such as intestinal fistulas and chronic wounds. These complications seriously impact outcomes due to mesh rigidity and its incompatibility with surrounding tissues. In this study, we designed a multifunctional hydrogel composed of GelMA (Gelatin Methacryloyl) and SilMA (Silk Fibroin Methacryloyl) as a promising solution for open abdominal wound repair. In vitro experiments confirmed the biocompatibility, self-healing properties, pro-angiogenic effects, and promotion of macrophage polarization. In vivo studies revealed that the GelMA-SilMA hydrogel could enhance abdominal wall tissue thickness and integrity via isolating the peritoneal cavity, protecting the intestinal tract, polarizing macrophages, promoting collagen formation, inducing neovascularization, inhibiting oxidative stress, and suppressing inflammation. Furthermore, immunofluorescence, immunohistochemistry, and RNA sequencing were employed to evaluate the wound healing mechanisms of GelMA-SilMA hydrogels. The results demonstrated that the hydrogels can promote angiogenesis, inhibit inflammation and immune responses, and enhance wound healing by activating the HIF-a-VEGF signaling pathway, RAP1 signaling pathway, and PI3K-AKT signaling pathway. Hence, the multifunctional GelMA-SilMA hydrogel has tremendous potential for clinical use in open abdominal wound repair.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
材料科学
·
外科技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Panpan Xue,Huilan Zhuang,Sijie Shao,Tingjie Bai,Xuemei Zeng,Shuangqian Yan
The activation of cellular ferroptosis is promising in tumor therapy. However, ferroptosis is parallelly inhibited by antiferroptotic substances, including glutathione peroxidase 4 (GPX4), dihydroorotate dehydrogenase (DHODH), and ferroptosis suppressor protein 1 (FSP1). Thus, it is highly desirable, yet challenging, to simultaneously suppress these three antiferroptotic substances for activating ferroptosis. Here, we rationally designed a hollow iron-doped SiO2-based nanozyme (FeSHS) loaded with brequinar (BQR) and lificiguat (YC-1), named FeSHS/BQR/YC-1-PEG, for tumor ferroptosis activation. FeSHS were developed through the continuous etching of SiO2 nanoparticles by iron ions, which exhibit pH/glutathione-responsive biodegradability, along with mimicking the activities of peroxidase, glutathione oxidase, and NAD(P)H oxidase. Specifically, glutathione depletion and NAD(P)H oxidation by FeSHS will suppress the expression of GPX4 and inhibit FSP1 by disrupting the NAD(P)H/FSP1/ubiquinone axis. In addition, the released BQR can suppress the expression of DHODH. Meanwhile, YC-1 is able to increase the cellular polyunsaturated fatty acids (PUFAs) by destroying the HIF-1α/lipid droplet axis. The elevation of levels of iron and PUFAs while simultaneously disrupting the GPX4/DHODH/FSP1 inhibitory pathways by our designed nanoplatform displayed high therapeutic efficacy both in vitro and in vivo. This work elucidates rationally designing smart nanoplatforms for ferroptosis activation and future tumor treatments.
研究领域:
纳米技术
·
癌症治疗
·
生物化学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Fanjia Dai,Jiaying Zhang,Fengjiao Chen,Xianwu Chen,Celine Jessica Lee,Hongze Liang,Lingling Zhao,Hui Tan
The repair of diabetic wound still encounters huge challenges, such as disordered inflammatory regulation and impaired neovascularization. Here, a pH/ROS/glucose responsive and photothermal hydrogel is developed for diabetic wound healing. The hydrogel is formed through cross-linkage between phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA) and oxide dextran (OXD), utilizing Schiff base and phenylboronate ester bonds. Additionally, insulin-like growth factor 1 C domain (IGF-1C) and deferoxamine-loaded polydopamine nanoparticles (D@P) are incorporated into the hydrogel. The hydrogel demonstrates sustained drug release, excellent photo thermal effect, prominent antioxidant, antibacterial and anti-inflammatory activities, desirable mechanical and tissue adhesive properties, enhanced tube formation, and cell migration. Furthermore, the hydrogel combined with mild heat treatment can regulate chronic inflammation by promoting the transformation of macrophages from M1 phenotype to M2 phenotype and enhance angiogenesis by up-regulating the expression levels of angiogenesis-related factors such as hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), CD31, and α-SMA, thus greatly accelerates the wound healing in streptozotocin (STZ)-induced diabetic mice. Therefore, this multi-responsive and multifunctional hydrogel holds potential as a therapeutic strategy for diabetic wounds.
研究领域:
材料科学
·
生物医学工程
·
药学
·
组织工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Maoxing Pan,Yuanjun Deng,Yebei Qiu,Dajin Pi,Chuiyang Zheng,Zheng Liang,Jianwei Zhen,Wen Fan,Qingliang Song,Jinyue Pan,Yuanyou Li,Haizhen Yan,Qinhe Yang,Yupei Zhang
Background Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. Purpose This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. Methods First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. Results We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. Conclusion Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.
研究领域:
药理学
·
分子生物学
·
代谢组学
·
营养学
✓ 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）