CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 41
·期 4
·525-537
·
IF 3.815
Zhou Meng-Xue,Zhang Jia-Yu,Cai Xiao-Meng,Dou Rui,Ruan Li-Fo,Yang Wen-Jiang,Lin Wen-Chu,Chen Jun,Hu Yi
As one of the major challenges in tumor chemotherapy, multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells. Herein, we design a kind of near-infrared (NIR) light- and acidity-activated micellar iPUTDN nanoparticle for mitochondria-targeting doxorubicin (DOX) delivery to combat DOX resistance in small-cell lung cancer. While the PEGylated iPUTDN nanoparticles can keep stealth in blood circulation, NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles, and the exposed iRGD can facilitate deep tumor penetration of the nanoparticles. After being internalized by DOX-resistant H69AR cells, the poly(β-aminoester)s (PAE)-based nanoparticles can release the triphenylphosphonium (TPP)-conjugated DOX (TDOX) into the cytosol, which can further accumulate in mitochondria with the aid of TPP. Consequently, the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells. The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Yajie Zhang,Peng-Hang Chen,Benhao Li,Huishan Guo,Junfei Zhu,Zechun Dang,Shan Lei,Peng Huang,Jing Lin
Chemodynamic therapy (CDT) is a highly tumor-specific treatment, while its efficacy is compromised by the intratumoral Fenton reaction efficiency, which is determined by the following reaction factors, including the availability of Fenton ions (e.g., Fe2+), the amount of H2O2, and the degree of acidity. Synchronous optimization of these factors is a big challenge for efficient CDT. Herein, a strategy of comprehensively optimizing Fenton reaction factors was developed for traceable multistage augmented CDT by charge-reversal theranostics. The customized pH-responsive poly(ethylene)glycol-poly(β-amino esters) (PEG–PAE) micelle (PM) was prepared as the carrier. Glucose oxidase (GOx), Fe2+, and pH-responsive second near-infrared (NIR-II) LET-1052 probe were coloaded by PM to obtain the final theranostics. The activity of metastable Fe2+ remained by the unsaturated coordination with PEG–PAE. Then tumor accumulation and exposure of Fe2+ were achieved by charge-reversal cationization of PEG–PAE, which was further enhanced by a GOx catalysis-triggered pH decrease. Together with the abundant H2O2 generation and pH decrease through GOx catalysis, the limiting factors of the Fenton reaction were comprehensively optimized, achieving the enhanced CDT both in vitro and in vivo. These findings provide a strategy for comprehensively optimizing intratumoral Fenton reaction factors to overcome the intrinsic drawbacks of current CDT.
研究领域:
癌症治疗
·
纳米医学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 114
·113209-113218
·
IF 3.289
Jun Yu,Feng Xiao,James Asenso,Peng Zhou,Xiao-Dan Yang,Chun Wang,Wei Wei
Paeoniflorin (Pae), a water-soluble monoterpene glucoside, is the main effective component of total glucoside of paeony (TGP). Pae has a very low bioavailability (3.6%). The aim of this study was to investigate the effects of sex, food and disease status on the pharmacokinetics of paeoniflorin-6′-O-benzene sulfonate (acylated derivative of Pae, CP-25) and its primary metabolite (Pae, M1) after oral administration in the plasma of rats. A specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for rapid determination of CP-25 and Pae in rat plasma was developed and validated for the first time. The assay was validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. We found that CP-25 had a more extensive distribution in females than that in males, but no differences in M1 levels were found. Food intake could also increase the extent of absorption and decrease the rate of clearance for CP-25 and M1 after oral administration in rats. The disease status would decrease the absorption of CP-25 in rats. Comparing single-doing and multiple-dosing in an adjuvant arthritis (AA) model, the absorption of CP-25 and M1 improved with increasing dosage. Furthermore, during the period of multiple-dosing, CP-25 exhibited a better anti-inflammatory effect in AA rats and no obvious side effects occurred during the dosing period. Our findings provide the basis, and some guidelines, for further studies into the clinical application of CP-25.
研究领域:
药理学
·
分析化学
·
临床医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Ning Wang,Nan Zhang,Mei-Ling Sun,Yan Sun,Qing-Yu Dong,Yu Wang,Zeng-Tian Gu,Hai-Tao Ding,Qi-Long Qin,Yong Jiang,Xiu-Lan Chen,Yu-Zhong Zhang,Chao Gao,Chun-Yang Li
Phthalate esters (PAEs) are emerging hazardous and toxic chemicals that are extensively used as plasticizers or additives. Diethyl phthalate (DEP) and dimethyl phthalate (DMP), two kinds of PAEs, have been listed as the priority pollutants by many countries. PAE hydrolases are the most effective enzymes in PAE degradation, among which family IV esterases are predominate. However, only a few PAE hydrolases have been characterized, and as far as we know, no crystal structure of any PAE hydrolases of the family IV esterases is available to date. HylD1 is a PAE hydrolase of the family IV esterases, which can degrade DMP and DEP. Here, the recombinant HylD1 was characterized. HylD1 maintained a dimer in solution, and functioned under a relatively wide pH range. The crystal structures of HylD1 and its complex with monoethyl phthalate were solved. Residues involved in substrate binding were identified. The catalytic mechanism of HylD1 mediated by the catalytic triad Ser140-Asp231-His261 was further proposed. The hylD1 gene is widely distributed in different environments, suggesting its important role in PAEs degradation. This study provides a better understanding of PAEs hydrolysis , and lays out favorable bases for the rational design of highly-efficient PAEs degradation enzymes for industrial applications in future.
研究领域:
环境科学
·
生物化学
·
酶学
·
结构生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2021
·
IF 5.121
Chunjing Guo,Yanguo Su,Bingjie Wang,Qiang Chen,Huimin Guo,Ming Kong,Daquan Chen
With the increasing number of oncology patients and the use of chemotherapeutic agents, tumour multidrug resistance is becoming more and more prevalent. The search for new tumour treatment strategies to overcome tumour multidrug resistance is urgent. In this study, we designed GSH and ROS dual-responsive tumour-associated macrophages (TAMs)-targeted nanoparticles (NPs) for the co-delivery of the clinical first-line anti-breast cancer chemotherapy drug paclitaxel (PTX) and baicalin (Bai), which re-educates TAMs to alter their phenotype. We synthesised oligohyaluronic acid-mannose-folic acid (oHA-Man-FA, HMF) and astragalus polysaccharide-dithiodipropionic acid-paeoniflorol (APS-S-Pae, ASP), two hybrid materials that can self-assemble in water to form hybrid nanoparticles (HP-NPs) co-loaded with paclitaxel and baicalin (HP-NPs@PTX/Bai). The experimental results show that our designed hybrid nanoparticles can be specifically released in the tumour microenvironment and deliver the antitumor drug PTX as well as Bai, which reshapes the phenotype of TAMs, to the tumour site. The hybrid nanoparticles not only effectively re-educated TAMs from M2 TAM to M1 TAM, but also ameliorated the cytotoxic side effects caused by free PTX and provided better tumour suppression than free PTX and HP.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
免疫治疗
✓ 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）