Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 29
·6001-6012
·
IF 4.726
Sen Lin,Fangfang Deng,Ping Huang,Lingli Li,Lei Wang,Qing Li,Ling Chen,Hao Chen,Kaihui Nan
Legumain is the only acidic asparaginly-endopeptidase in mammals that is highly up-regulated in tumor tissue and tumor associated cells. In this study, a novel legumain protease-activated micelle was successfully synthesized and prepared by loading with doxorubicin (DOX). The prepared micelle exhibited a spherical morphology and possessed a low critical micelle concentration of 1.21 × 10−3 mg mL−1 with a DOX loading capacity and entrapment efficiency of 4.05% and 60.6% respectively. The release profile of DOX from this micelle formulation was observed to be legumain concentration dependent. The micelle encapsulation of DOX highly enhanced the cellular uptake of DOX by tumor cell lines of DAOY, Y79, MCF-7, and MCF-7/DOX. Furthermore, encapsulation of DOX boosts the cytotoxicity against the tumor cells while reducing cytotoxicity against RPE and HEK293 cells. In addition, blank micelles did not exhibit any biological effects on tumor or RPE or HEK293 cells at the concentration range of 0–300 μg mL−1, indicating good biocompatibility. The results suggest that this micelle formulation has potential applications in sustained drug delivery for legumain up-regulated tumors.
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Ling Qiu,Xi Li,Gaochao Lv,Yann Seimbille,Ke Li,Ying Peng,Qingzhu Liu,Minhao Xie,Jianguo Lin
Overexpression of legumain is closely associated with tumor proliferation, invasion, and metastasis. Because of its intrinsic properties, such as high sensitivity and resolution, positron emission tomography (PET) has become an effective imaging technique for early diagnosis, treatment response prediction, and monitoring. Herein, two legumain-targeting radiofluorinated smart probes (18F-2 and 18F-3) as well as a control probe (18F-1) were specifically designed for PET imaging of legumain activity in tumors. 18F-1, 18F-2, and 18F-3 were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient “one-step” 18F-labeling method. The probes 18F-2 and 18F-3 exhibited high response to legumain activity and reductive environment and revealed comparable uptake in HCT116 cells (4.22% ± 0.14% and 4.64% ± 0.32% for 18F-2 and 18F-3, respectively; 8.46% ± 0.33% and 9.05% ± 0.24% for co-treatment of 18F-2 + 2 and 18F-3 + 3 at 1 h), while the control probe 18F-1 showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy (18F-2 + 2 and 18F-3 + 3) resulted in higher tumor uptake (3.57% ± 0.37% and 3.72% ± 0.19% ID/g at 10 min, respectively) than the single injection strategy (2.59% ± 0.19% and 2.60% ± 0.46% ID/g for 18F-2 and 18F-3, respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to 18F-3 reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that 18F-3 holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors.
研究领域:
医学成像
·
癌症研究
·
分子生物学
·
放射学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Ke Li,Ruxiang Li,Pengfei Zou,Li Li,Huajun Wang,Deqian Kong,Guangying Zheng,Li-Li Li
Efficient and non-invasive drug delivery to the fundus has always been a medical difficulty. Here, a co-assembled glycopeptide nanotransforrs (GPNTs) named [email protected] as a drug delivery system is reported. The [email protected] co-assemble nanoparticles consisting of glycopeptide, cationic peptide, and doxorubicin (DOX). The nanoparticles are positively charged with the nano-size, which can be induced transformation by legumain cleavage. Once administrate to the eyes, [email protected] has a high penetration through the ocular surface to specifically targets M2 macrophages in the fundus. Then, the mannose receptor mediates phagocytosis and intracellular highly expressed legumain induces its nanofibrous transformation, which contributes to a 44.7% DOX retention in cells at 24 h than that of the non-transformed controls ( [email protected] : 5.1%). The nanofiber transformation provides an inhibition of exocytosis, which explains the higher retention of the delivered drug. In the mouse OIR model, [email protected] completely restores the physiological angiogenesis and reduces pathological neovascularization . Pathological neovascularization branches and cell nuclei that break through the inner limiting membrane are reduced by 55% and 72%, respectively, which are 25% and 20% less than those in the non-transformed controls. In addition, [email protected] also has good histocompatibility , which provides a possible strategy for non-invasive treatment of fundus diseases in the future.
研究领域:
药学
·
纳米技术
·
眼科
·
药物递送系统
·
生物医学工程
✓ 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）