JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Jiaojiao Wu,Xueyan Wei,Zhenguang Li,Haotian Chen,Rui Gao,Peng Ning,Yingze Li,Yu Cheng
Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo . This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors.
研究领域:
癌症生物学
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纳米技术
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生物医学工程
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 9
·1403-1409
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IF 7.571
Ying Chen,Jiahui Zan,Yong Liu,Peipei Kuang,Chunmei Guo,Chen Xie,Wei Huang,Quli Fan
Chemodynamic therapy (CDT) is a kind of novel cancer treatment with minimal side effects. As the therapeutic efficacy of a single CDT is usually not satisfactory, combining other therapeutic modalities with CDT is commonly used to improve the therapeutic efficacy. However, such kinds of combination therapeutic systems may suffer from the issue of side effects. Herein, we report a pH-triggered chemodynamic/chemo combination therapeutic nanomedicine based on CeO2–MnO2 nanorods (CMNRs). Such a nanomedicine (DOX@PCMNR-RGD) is prepared by coating RGD-conjugated charge-reversal polymers onto the surface of CeO2–MnO2 nanoparticles, followed by loading doxorubicin (DOX) onto it. Under mild acidic conditions, the surface charge of nanomedicine may change from negative to positive because of the charge-reversal polymer, making it easy to be internalized into cells. In addition, the tumor overexpressed hydrogen peroxide (H2O2) can be selectively catalyzed into highly toxic hydroxyl radicals (˙OH) under acidic conditions by DOX@PCMNR-RGD, showing CDT activity. Meanwhile, the acidic condition can trigger the release of DOX, showing chemotherapeutic activity. Thus, our study provides a pH-triggered chemodynamic/chemo combination therapeutic nanoplatform with minimal side effects.
研究领域:
纳米技术
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癌症治疗
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材料科学
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药学
✓ 已验证
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
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IF 7.328
Mingyue Wang,Chenxi Wang,Yu Zhang,Ye Lin
Bone diseases, for example, osteoporosis, cause excessive differentiation of osteoclasts and decreased bone formation, resulting in imbalance of bone remodeling and poor osseointegration, which can be considered a relative contraindication for titanium implants. Dopamine (DA) might provide a solution to this problem by inhibiting osteoclasts and promoting osteoblasts at different concentrations. However, current commercial implants cannot load bone-active molecules, such as DA. Therefore, this study aimed to develop a surface modification method for implants to achieve a controlled release of DA and enhance the resistance of titanium implants to bone resorption and bone regeneration. DA-loaded alginate-arginine-glycine-aspartic acid (RGD) (AlgR) coatings on a vaterite-modified titanium surface were successfully assembled, which continuously and steadily released DA. In vitro studies have shown that materials showing good biocompatibility can not only inhibit receptor activator of nuclear factor-kappa B (NFκB) ligand (RANKL)-induced osteoclastogenesis but also enhance the adhesion and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The optimal DA-loaded concentration of this bidirectional regulation is 100 μM. Interestingly, DA more effectively attenuated osteoclastogenesis when released in a sustained manner from titanium coatings than it did via traditional, free administration, and the alginate-RGD coating and DA clearly exhibited great synergy. This study provides a design of titanium implant surface modification to improve bone remodeling around implants.
研究领域:
生物材料
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组织工程
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骨科
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生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Jianqing Peng,Qin Wang,Jia Zhou,Shuli Zhao,Pan Di,Yan Chen,Ling Tao,Qianming Du,Xiangchun Shen,Yi Chen
Antimalarial drugs Dihydroartemisinin (DHA) and chloroquine phosphate (CQ) exhibit evident anti-cancer activity, particularly as combination therapy. DHA and CQ combination therapy has been proved to exhibit higher cytotoxic effect in tumor cells and lower toxicity to normal cells than combination of artemisinin derivatives (ARTs) and anticancer chemotherapy drugs. However, different physiochemical properties of DHA and CQ, leading to distinctive in vivo outcomes, considerably limited their synergistic effect in cancer treatment. Herein, we developed a lipid nanoparticle (LNP) for co-delivery of DHA and CQ to inhibit proliferation and metastasis of colorectal cancer. Considering the beneficial effects of acid/reactive oxide species (ROS)-sensitive phospholipids and targeting ligands for colorectal cancer cells, an RGD peptide-modified pH/ROS dual-sensitive LNP loaded with DHA and CQ (RLNP/DC) was prepared. It exhibited optimal cytotoxicity and suppression of invasion and metastasis in HCT116 cells in vitro , attributable to irreversible upregulation of intracellular ROS levels, downregulation of VEGF expression, and upregulation of paxillin expression. A mouse model of orthotopic metastasis of colorectal cancer was established to evaluate anti-proliferation and anti-metastasis effects of RLNP/DC in vivo . Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer.
研究领域:
药学
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肿瘤学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2023
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IF 9.7
Yuan Chen,Zhuo Yao,Peilian Liu,Qida Hu,Yong Huang,Li Ping,Fu Zhang,Honglin Tang,Tao Wan,Yuan Ping,Bowen Li
Chemotherapeutics have been recommended as the standard protocol for inoperable patients with triple-negative breast cancer (TNBC) at advanced stage, yet limited success has been achieved in prolonging survival rates by this monotherapy. A major reason for this failure is the chemo-resistance from traditional apoptotic pathways resulting in poor therapeutic effect. Ferroptosis has become a powerful modality of no-apoptotic cell death, which can effectively evade chemo-resistance in apoptotic pathways. Herein, we propose an active-targeting small-molecular self-assembly nano-prodrug for co-delivery of chemotherapeutics (CPT), Ferrocene (Fc) and GPX4 inhibitor (RSL3) to overcome the chemo-resistance from traditional apoptotic pathways. In this nano-prodrug, the disulfide linkage not only serves as a GSH-responsive trigger, but also exhibits a stable self-assembly behavior that forms nanoparticle . Interestingly, the RSL3 can be loaded during this self-assembly process that forms a three-components nano-prodrug. In tumor environment, the high GSH level can disassemble the nano-prodrug to trigger the release of the parent drug, which can improve the therapeutic effect by synergistic effects of ferroptosis and apoptosis. In different TNBC mice models, the nano-prodrug is encapsulated into RGD-modified phospholipid micelles (DSPE-PEG2000-RGD) and exhibits high anti-tumor and anti-metastasis efficacy, especially in orthotopic models. The application of ferroptosis to assist the enhancement of chemotherapeutics may serve as a promising strategy for TNBC treatment. Statement of significance Chemotherapeutics have been recommended as the standard of care for palliative and adjuvant treatment in patients with triple-negative breast cancer (TNBC), yet limited success has been achieved in prolonging the overall survival of patients by this monotherapy. A major reason for this failure is the chemo-resistance from traditional apoptotic pathways resulting in poor therapeutic effect. Thus, the co-delivery of the apoptosis and ferroptosis drug may overcome or evade the resistance in chemotherapy-induced apoptotic pathways and provide a promising strategy to combat TNBC. In this work, we developed a small-molecular self-assembly nano-prodrug for co-delivery of chemotherapeutics (CPT), Ferrocene (Fc) and ferroptosis resistance inhibitor (RSL3), which could overcome the chemo-resistance and improve the therapeutic effect by synergistic effects of ferroptosis and apoptosis.
研究领域:
肿瘤学
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药物科学
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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·10646-10646
·
IF 3.8
Qinghua Xie,Xuemei Wang,Gaorui Zhang,Dawei Zhou,Yuxuan Zhao,Hong Liu,Jiazhi Duan,Dexin Yu,Yuanhua Sang
Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe 3 O 4 nanoclusters were developed for tumor-targeted dual-mode T 1 /T 2 -weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe 3 O 4 nanoclusters synthesized by facilely modifying ultrasmall Fe 3 O 4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe 3 O 4 nanoclusters shows excellent dual-mode T 1 and T 2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe 3 O 4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe 3 O 4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.
研究领域:
纳米技术
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生物医学工程
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分子影像
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癌症治疗
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Yu Zhao,Huangmei Zhou,Longliang Qiao,Jinming Xu,Rodolphe Antoine,Lunhua Deng,Sanjun Zhang,Haifeng Ye
Precise measurements of tumor pH is essential for early cancer diagnose, treatment planning, and the development of anti-cancer drugs. Herein, we present a pH-sensitive, ratiometric fluorescent biosensor with tumor-targeting capabilities for real-time in vivo tumor pH detection. The biosensor, composed of glutathione-protected gold nanoclusters (AuNCs) conjugated with fluorescein-isothiocyanate (FITC), provides a reliable ratiometric fluorescence signal response to pH. The cyclic arginine-glycine-aspartic acid (c(RGDyC)) peptide was integrated into the sensor (denoted as c(RGDyC)-FITC@AuNCs) to confer tumor-targeting specificity. Upon excitation at 488 nm, c(RGDyC)-FITC@AuNCs exhibited dual-channel emissions at 515 nm and 710 nm, the ratio of which showed a 17-fold change across a pH range of 5.5 to 8.0. In addition, c(RGDyC)-FITC@AuNCs demonstrated excellent biocompatibility, long-term photostability, and low toxicity, enabling the quantitative monitoring of the pH changes during tumor cell apoptosis in real-time. Moreover, using tumor-bearing mouse models with induced acid-alkaline variations, c(RGDyC)-FITC@AuNCs successfully visualized and dynamically tracked in situ tumor pH. This biosensor offers a sensitive and accurate tool for tumor diagnosis, with significant potential in biomedical research and clinical studies.
研究领域:
生物医学工程
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纳米技术
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生物化学
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癌症研究
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分子成像
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荧光传感
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药学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
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2024
·
IF 14.3
Xing-wang Wang,Yi-jing Yin,Jing Wang,Hong-mei Yu,Qian Tang,Zhao-yang Chen,Guo-sheng Fu,Ke-feng Ren,Jian Ji,Lu Yu
The left atrial appendage (LAA) occluder is an important medical device for closing the LAA and preventing stroke. The device-related thrombus (DRT) prevents the implantation of the occluder in exerting the desired therapeutic effect, which is primarily caused by the delayed endothelialization of the occluder. Functional coatings are an effective strategy for accelerating the endothelialization of occluders. However, the occluder surface area is particularly large and structurally complex, and the device is subjected to a large shear friction in the sheath during implantation, which poses a significant challenge to the coating. Herein, a hydrogel coating by the in situ UV-triggered polymerization of double-network polyelectrolytes is reported. The findings reveal that the double network and electrostatic interactions between the networks resulted in excellent mechanical properties of the hydrogel coating. The sulfonate and Arg-Gly-Asp (RGD) groups in the coating promoted hemocompatibility and endothelial growth of the occluder, respectively. The coating significantly accelerated the endothelialization of the LAA occluder in a canine model is further demonstrated. This study has potential clinical benefits in reducing both the incidence of DRT and the postoperative anticoagulant course for LAA closure.
研究领域:
生物医学工程
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材料科学
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心血管医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jiahui Yan,Haoyu Chen,Carlos F. Guimarães,Rui L. Reis,Zhihua Zhu,Tianyi Wang,Fenglan Zhang,Yaqian Lv,Qihui Zhou,Xiaoying Kong,Jinsheng Shi
Ion interference including copper (Cu + )/calcium (Ca 2+ ) overload activate cell-specific death channels, damage mitochondria and disrupt cellular homeostasis, showing great potential in anti-tumor therapy. However, the complex metabolic environment and the powerful self-protection of tumors cause clinical failure of ion interference. Thus, metabolic disruption is expected an innovative strategy for the enhancement of ion interference. Herein, CuS-α-CHCA&penthiopyrad@CaCO 3 -RGD nanoparticles (CCPCR NPs) are prepared to provide a Cu + /Ca 2+ dual-overload anti-tumor therapy assisted by metabolic-symbiosis-destruction strategy, realizing the collapse of tumor self-protection. Specifically, precise CuS and CaCO 3 delivery triggered irreversible Cu + /Ca 2+ dual-overload and reactive oxygen species (ROS) attack toward 4T1 cells. Meanwhile, α-CHCA and penthiopyrad disturbed the metabolic symbiotic environment by disrupting the TCA cycle and preventing lactate efflux to aggravate intracellular acidosis and promote Fenton-like reaction of Cu + , enhancing the sensitivity of tumor cells to copper death and Ca 2+ overload. Further, aided by the metabolism of symbiosis, the destroyed tumor cells further activate the polarization of M1 macrophages and the maturation and antigen cross-presentation of dendritic cells (DCs), which further eliminate tumor cells. In summary, an amplified anti-tumor dual-ion interference strategy assisted by metabolic symbiotic destruction is established, which is of great significance in improving the clinical effect of ion therapy for tumors.
研究领域:
肿瘤学
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药学
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免疫学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jing Zhang,Ximeng Sun,Yongyuan Heng,Yunfeng Zeng,Yijia Wang,Yu Shen,Anhui Peng,Wenzhe Tang,Ming Zeng,Ziyi Yu
The utilization of hydrogels for DNA/cationic polymer polyplex nanoparticle (polyplex) delivery has significantly advanced gene therapy in tissue regeneration and cancer treatment. However, persistent challenges related to the efficacy and safety of encapsulated polyplexes, stemming from issues such as aggregation, degradation, or difficulties in controlled release during or postintegration with hydrogel scaffolds, necessitate further exploration. Here, we introduce an injectable gene therapy gel achieved by incorporating concentrated polyplexes onto densely packed hydrogel microparticles (HMPs). Polyplexes, when uniformly adhered to the gene therapy gel through reversible electrostatic interactions, can detach from the HMP surface in a controlled manner, contrasting with free polyplexes, and thereby reducing dose-dependent toxicity during transfection. Additionally, the integration of RGD cell adhesion peptides enhances the scaffolding characteristics of the gel, facilitating cell adhesion, migration, and further minimizing toxicity during gene drug administration. Notably, despite the overall transfection efficiency showing average performance, utilizing confocal microscopy to meticulously observe and analyze the cellular states infiltrating into various depths of the gene therapy gel resulted in the groundbreaking discovery of significantly enhanced local transfection efficiency, with primary cell transfection approaching 80%. This phenomenon could be potentially attributed to the granular hydrogel-mediated delivery of polyplex nanoparticles, which revolutionizes the spatial and temporal distribution and thus the “encounter” mode between polyplexes and cells. Moreover, the gene therapy gel’s intrinsic injectability and self-healing properties offer ease of administration, making it a highly promising candidate as a novel gene transfection gel dressing with significant potential across various fields, including regenerative medicine and innovative living materials.
研究领域:
生物医学工程
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基因治疗
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组织工程
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2020
·
IF 5.115
Xiang Li,Qian Zou,Jing Zhang,Peng Zhang,Xiong Zhou,Satya Siva Kishan Yalamarty,Xinli Liang,Yali Liu,Qin Zheng,Jianqing Gao
Purpose Folic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated. Materials and Methods The temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD + /NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated. Results The sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD + /NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis. Conclusion E/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.
研究领域:
肿瘤学
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纳米技术
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药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL DESIGN
·
2023
·
IF 3.1
Yi Shi,Qian Wu,Yi Lu,Ling-Peng Meng,Xiao-Ling Xu,Xiao-Juan Wang,Wei Chen
Aim We aimed to design RGD-anchored liposomes encapsulating an antipyroptosis drug that could efficiently target macrophages and relieve the rate of cytokine release syndrome, providing a new strategy for sepsis treatment, especially sepsis-induced acute renal injury. Background Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by host response disorders due to infection. Sepsis has a high incidence and remains one of the leading causes of death worldwide. Objective Macrophage-mediated pyroptosis plays an important role in the occurrence and development of cytokine release syndrome and organ injury caused by sepsis. Curcumin can inhibit inflammasome assembly and slow the progression of pyroptosis by scavenging intracellular reactive oxygen species, but it has poor water solubility and low bioavailability. The emergence of drug-delivery nanosystems has overcome this problem, but there is still a lack of research on how to accurately deliver antipyroptotic drugs to innate immune cells and subsequently hinder pyroptosis. Methods We constructed a curcumin-loaded RGD-modified liposome (RGD-lipo/Cur) and demonstrated that RGD-lipo/Cur could effectively target macrophages. Results In vitro , RGD-lipo/Cur reduced the upregulation of caspase-1, caspase-3, NLRP3, IL-1β and GSDMD, inhibiting pyroptosis, reducing oxidative stress, and attenuating the proinflammatory cytokine cascade. Conclusion RGD-lipo/Cur was considered to have great potential for sepsis treatment.
研究领域:
药理学
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纳米技术
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免疫学
·
临床医学
✓ 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）