JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2015
·
IF 3.368
Jingjing Zhao,Bo Zhang,Shun Shen,Jun Chen,Qizhi Zhang,Xinguo Jiang,Zhiqing Pang
Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS) tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the glioblastoma parenchyma were crucial challenges in GBM nanomedicine therapy. Nanoparticle diameter can significantly influence the delivery efficiency in tumor tissue. Decreasing nanoparticle size can improve the nanoparticle penetration in tumor tissue but decrease the nanoparticle retention effect. Therefore, small nanoparticles with high retention effect in tumor are urgently needed for effective GBM drug delivery. In present study, a small nanoparticle drug delivery system was developed by conjugating fibrin-binding peptide CREKA to Polyamidoamine (PAMAM) dendrimer , where PEGylated PAMAM is used as drug carrier due to its small size and good penetration in tumor and CREKA is used to target the abundant fibrin in GBM for enhanced retention in tumor. In vitro binding ability tests demonstrated that CREKA can significantly enhanced nanoparticle binding with fibrin. In vivo fluorescence imaging of GBM bearing nude mice, ex vivo brain imaging and frozen slices fluorescence imaging further revealed that the CREKA-modified PAMAM achieved higher accumulation and deeper penetration in GBM tissue than unmodified one. These results indicated that the CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for brain tumor therapy.
研究领域:
肿瘤学
·
药剂学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2024
·
IF 4
Ningxin Yang,Yuelin Huang,Xiaoyu Wang,Dengbin Wang,Defan Yao,Gang Ren
The prevalence and fatality rates of gastric cancer (GC) remain elevated, with advanced stages presenting a grim prognosis. Noninvasive diagnosis of GC cancer often proves challenging until the disease has progressed to an advanced stage or metastasized. Initially, the level of fibronectin (FN) in cancer-associated fibroblasts (CAFs) of GC was at least 3.7 times higher than that in normal fibroblasts. Herein, two FN-targeting magnetic resonance/near-infrared fluorescence (MR/NIRF) imaging contrast agents were developed to detect GC and peritoneal metastasis noninvasively. The probes CREKA-Cy7-(Gd-DOTA) and CREKA-Cy7-(Gd-DOTA)3 demonstrated significant FN-targeting capability (with dissociation constants of 1.0 and 2.1 mM) and effective MR imaging performance (with proton relaxivity values of 9.66 and 27.44 mM–1 s–1 at 9.4 T, 37 °C). In vivo imaging revealed a high signal-to-noise ratio and successful visualization of GC metastasis using NIRF imaging as well as successful tumor detection in MR imaging. Therefore, this study highlights the potential of FN-targeting probes for GC diagnosis and aids in the advancement of new diagnostic strategies for the clinical detection of GC.
研究领域:
医学影像学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2025
·
IF 5.1
Yaxue Liu,Yu Li,Junlong Chen,Pei Xie,Zongning Yin
The clinical application of conventional thrombolytic drugs is limited due to the difficulty in precisely targeting the thrombus site and side effects such as severe bleeding. In order to specifically image thrombus for diagnosis and thrombolytic therapy, a CREKA-targeted and pH-responsive drug release nano-delivery system, called LK/PDB/IR820-CREKA NPs, was constructed. In vitro experiments showed that NPs had good pH responsiveness and biocompatibility. The in vitro thrombolytic rate was as high as 46% and had a strong thrombus-binding ability. In the FeCl3-induced carotid artery thrombosis model in mice, PDB/IR820-CREKA NPs could specifically target thrombus, which enabled accurate diagnosis of thrombus sites. Targeted nanoparticle-encapsulated Lumbrokinase at a dose of 900 U/10g significantly reduced the total protein content at the thrombus site, while reducing the risk of non-specific bleeding. Based on the thrombus-specific imaging and therapeutic activity, this nano-delivery system has the potential to be used for the treatment of thrombotic vascular diseases.
研究领域:
医学
·
药学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Minxia Zhu,Luwen Zhu,Yuchan You,Mingchen Sun,Feiyang Jin,Yanling Song,Jucong Zhang,Xiaoling Xu,Jiansong Ji,Yongzhong Du
Tumor interstitial pressure represents the greatest barrier against drug diffusion into the depth of the tumor. Biometric nanomotors highlight the possibility of enhanced deep penetration and improve cellular uptake. However, control of their directionality remains difficult to achieve. Herein, we report cysteine-arginine-glutamic acid-lysine-alanine (CREKA)-modified ceria@polydopamine nanobowls as tumor microenvironment-fueled nanoscale motors for positive chemotaxis into the tumor depth or toward tumor cells. Upon laser irradiation, this nanoswimmer rapidly depletes the tumor microenvironment-specific hydrogen peroxide (H2O2) in the nanobowl, contributing to a self-generated gradient and subsequently propulsion (9.5 μm/s at 46 °C). Moreover, the asymmetrical modification of CREKA on nanobowls could automatically reconfigure the motion direction toward tumor depth or tumor cells in response to receptor–ligand interaction, leading to a deep penetration (70 μm in multicellular spheroids) and enhanced antitumor effects over conventional nanomedicine-induced chemo-photothermal therapy (tumor growth inhibition rate: 84.2% versus 56.9%). Thus, controlling the direction of nanomotors holds considerable potential for improved antitumor responses, especially in solid tumors with high tumor interstitial pressure.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Ni Fang,Jia Liu,Jingxin Hou,Yixin Zhong,Ying Luo,Liu Hu,Wenli Zhang,Junrui Wang,Jie Xu,Jun Zhou,Yu Zhang,Haitao Ran,Dajing Guo
Background Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability.Materials and Methods In the bionic system, gelatin was chosen as a carrier, and Fe3O4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide.Results In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in vivo. Moreover, compared with the bionic system group, the group treated with TNPs had significantly decreased liver and spleen signals in MR images and significantly enhanced liver and spleen signals in fluorescence images, indicating that the bionic system is less likely to be cleared by the reticuloendothelial system (RES) than TNPs, which may promote the accumulation of the bionic system at the site of the thrombus.Conclusion These results suggest that the magnet-guided bionic system with LIFU responsiveness is an excellent candidate for targeting thrombi and holds promise as an innovative drug delivery system for thrombolytic therapy.
研究领域:
医学
·
纳米生物技术
·
影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yina Su,Linjie Huang,Guizhen Xu,Simin Chen,Jiaqiong Wu,Siyu Wang,Yichao Zhang,Xiahui Lin
Traditional antithrombotic therapeutic strategies encounter challenges including heightened bleeding risks, short circulation times, low targeting ability, and inferior thrombus penetration. Therefore, a novel thrombolysis nanodrug (APBUL) is designed that incorporates urokinase (UK) loaded onto the surface of bowl-shaped nanomotors (APBs) encapsulated within fibrin peptide (CREKA)-modified thermosensitive liposomes, presenting an innovative therapeutic platform for thrombolysis. APBUL leverages CREKA's targeting ability for thrombus accumulation. Subsequently, under the irradiation of near-infrared light, the thermosensitive liposomal shell undergoes controlled disruption, releasing internal APBs and UK. Then, the APBs move directionally though thermophoresis effect, facilitating photothermal therapy and deep thrombus penetration, and synergistically enhancing UK release and diffusion to optimize thrombolysis. Moreover, the APBUL possesses a catalase-like activity, catalyzing hydrogen peroxide into oxygen to alleviate oxidative stress and inflammatory factors at the thrombus site, thereby lowering the recurrence risk. Combined with the ability of APBUL's photoacoustic imaging, this new strategy is expected to provide an inspiring idea for the integrated use of clinical thrombolytic therapy in diagnosis, imaging, and treatment.
研究领域:
生物医学工程
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纳米医学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 7
·2359-2371
·
IF 6.6
Alimina Awen,Dehong Hu,Duyang Gao,Zihang Wang,Yayun Wu,Hairong Zheng,Lina Guan,Yuming Mu,Zonghai Sheng
Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine–arginine–glutamate–lysine–alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.
研究领域:
医学成像
·
心血管疾病
·
分子生物学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Huijuan Zhang,Kexuan Cao,Chaoqun Wang,Yingmei Tian,Lin Hou
Drug thrombolysis is the main means of clinical treatment for thrombotic-related diseases. However, serious bleeding complications caused by low drug delivery efficiency and secondary vascular embolism usually lead to unsatisfactory therapeutic effects. Herein, we constructed a thrombin and near-infrared (NIR) dual-responsive drug-loaded intelligent system to solve the above problems. The CREKA-modified polydopamine (PDA) nanoparticles (NPs) were crosslinked by thrombin-responsive peptide (Pep), to obtain Pep-PPC nanocarriers with special mesoporous nanostructures. Subsequently, NO donor BNN6 and thrombolytic drug UK were loaded on the surface and into the mesoporous of Pep-PPC, to get the multifunctional Pep-NO@PPC/UK. In vitro and in vivo results proved that Pep-NO@PPC/UK could effectively recognize and aggregate at the thrombus site via CREKA-mediated active targeting. Then local abundant thrombin cleaved the nanoplatform to release UK. Meanwhile, PDA converted NIR light into heat and synchronously triggered NO release. This transformed the DDS into a “heat-gas” dual propulsion nanomotor in situ, driving deep penetration of UK in thrombus tissue. Under the combined action of UK and PTT, arterial thrombosis rapidly dissolved with relatively low bleeding risk. More importantly, NO generated in situ could prevent re-embolism of blood vessels at the thrombolytic site by inhibiting activated platelet aggregation, ultimately improving vascular reperfusion rate through a combination of attack and defense mode.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Mengjuan Sun,Chang Liu,Ji Liu,Jing Wen,Tianjiao Hao,Daquan Chen,Yan Shen
Thrombus-induced cardiovascular diseases threaten human health. Current treatment strategies often rely on urokinase plasminogen activator (uPA) for its efficacy, yet it has such limiting factors as short half-life, lack of thrombus targeting, and systemic side effects leading to unintended bleeding. In addition, thrombolytic interventions can trigger inflammation-induced damage at thrombus sites, which affects endothelial function. To address these challenges, Fer-1/uPA@pep-CREKA-Lipo (Fu@pep-CLipo) has been developed. This system achieves precise and efficient thrombolysis while enhancing the thrombus microenvironment and mitigating ischemia-reperfusion injury, with exceptional thrombus targeting ability via the strong affinity of the Cys-Arg-Glu-Lys-Ala (CREKA) peptide for fibrin. The Cys-Nle-TPRSFL-DSPE (pep) could respond to the thrombus microenvironment and fixed-point cleavage. The uPA component linked to the liposome surface is strategically cleaved upon exposure to abundant thrombin at thrombus sites. Importantly, the inclusion of Fer-1 within Fu@pep-CLipo contributes to reactive oxygen species (ROS) scavenging and significantly improves the thrombus microenvironment. This innovative approach not only achieves highly efficient and precise thrombolysis but also positively influences the expression of eNOS protein while suppressing inflammatory factors like TNF-α and IL-6. This dual action contributes to improved thrombus inflammatory microenvironment and mitigated ischemia-reperfusion injury.
研究领域:
心血管疾病
·
药学
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Chao Li,Yuxing Wu,Qinjun Chen,Yifan Luo,Peixin Liu,Zheng Zhou,Zhenhao Zhao,Tongyu Zhang,Boyu Su,Tao Sun,Chen Jiang
Reperfusion injury presents a significant obstacle to neuronal survival following successful recanalization in ischemic stroke, which is characterized by intricate pathophysiological processes comprising numerous interconnected pathways. Oxidative stress-induced neuronal ferroptosis and the overactivation of glial cells play important roles in this phenomenon. In this study, we developed a targeted cross-linked micelle loaded with idebenone to rescue the ischemic penumbra by inhibiting neuronal ferroptosis and glial overactivation. In rat models, the CREKA peptide-modified micelles accumulate in the damaged brain via binding to microthrombi in the ipsilateral microvessels. Upon reactive oxygen species (ROS) stimulation, diselenide bonds within the micelles are transformed to hydrophilic seleninic acids, enabling synchronized ROS consumption and responsive drug release. The released idebenone scavenges ROS, prevents oxidative stress-induced neuronal ferroptosis, attenuates glial overactivation, and suppresses pro-inflammatory factors secretion, thereby modulating the inflammatory microenvironment. Finally, this micelle significantly reinforces neuronal survival, reduces infarct volume, and improves behavioral function compared to the control groups. This pleiotropic therapeutic micelle provides a proof-of-concept of remodeling the lesion microenvironment by inhibiting neuronal ferroptosis and glial overactivation to treat cerebral ischemia-reperfusion injury.
研究领域:
神经科学
·
药学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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