NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 44
·21235-21244
·
IF 3.925
Huan Xu,Mingyue Yang,Yijing Du,Tian Gao,Yi Liu,Liwei Xiong,Na Peng
Nano-drug carriers have been widely used in chemotherapy to improve the efficacy of chemotherapeutic drugs. Polymer nano-carriers have greater potential for the enrichment of chemotherapeutic drugs at the target tumor site and controlled release. Herein, a series of amphiphilic copolymers (ITT) was synthesized via melt polymerization with a ROS-cleavable thioketal cross-linker, imidazole groups, and polyethylene glycol-conjugated triphenylphosphonium (PEG-TPP) segments; the actual proportions of the imidazole groups to the PEG-TPP segments were 5.2 : 1, 2.6 : 1, and 1.8 : 1, respectively. The amphiphilic copolymers could self-assemble into cationic micelles with hydrophobic imidazole groups as the core and hydrophilic PEG-TPP segments as the shell in deionized water. The cationic micelles with an average particle size of 124.6–187.3 nm showed a drug loading content (DLC) of 5.65–6.10%. In vitro release studies revealed the pH/ROS dual-responsiveness of the DOX-loaded ITT micelles, and the release behavior of DOX from the micelles strongly depended on the content of imidazole groups in the ITT micelles. Typically, the release of the encapsulated DOX was 27.2%, 30.0%, and 34.1% from DOX-loaded ITT-1 micelles in PBS (pH 6.5) containing 0, 100, and 500 μM H2O2, respectively. The release of the encapsulated DOX was 20.3%, 27.2%, and 42.5% from DOX-loaded ITT-1 micelles in PBS (pH 7.4), PBS (pH 6.5), and PBS (pH 5.0), respectively. The DOX-loaded micelles effectively inhibited the growth of 4T1 cells through being internalized into the 4T1 cells and releasing DOX into the mitochondria, with a cell viability of less than 65% when the DOX concentration was 2.5 μg mL−1. This work presents a novel mitochondria-targeting and pH/ROS-responsive polymer nanocarrier for potential chemotherapy applications.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Ning Zhang,Daquan Wang,Xunan Jing,Tingting Yang,Hongbo Yang,Lingjie Meng
In the past decades, polymer–drug conjugates of anticancer agents have gained much attention due to their enhanced aqueous solubility, improved pharmacokinetics, and better drug utilization than their conventional insoluble counterparts. Several polymer–drug conjugates have entered the third phase of clinical trials yet suffer from inherent deficiencies, including uncontrolled drug release and unclear degradation mechanisms. In this study, a pH/reactive oxygen species (ROS) dual-responsive PEG-doxorubicin (DOX) conjugate (denoted as TPD) was synthesized through acyl alkynyl-amine click reaction by PEG dipropiolate (PEGB), amine-terminated thioketal (TKL), and doxorubicin (DOX). Due to the generated ene-amine and thioketal in the backbone, the prepared amphiphilic TPD not only has a high drug loading ratio for photosensitizer chlorin e6 (Ce6) but also has the sensitivity to the acidic tumor microenvironment (TME) and ROS. Considering the complex conditions of TME, the prepared TPD@Ce6 nanoparticles (NPs) might respond to the relatively low pH and release Ce6 initially, and upon laser radiation, Ce6 produces abundant singlet oxygen (1O2) to achieve a programmable accelerated release of DOX and more Ce6 at the tumor site. In addition, the NIR fluorescence of DOX could monitor drug delivery and controlled release. The developed TPD@Ce6 NPs can realize the targeted tumor in combination therapy with negligible cytotoxicity on normal tissues.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
ACS Applied Nano Materials
·
2024
·
IF 5.3
Fanjia Dai,Fengjiao Chen,Jiaying Zhang,Xianwu Chen,Hongze Liang,Zhenjiang Liang,Shun Zhang,Hui Tan,Lingling Zhao
The tumor microenvironment is distinguished from normal tissues, such as the acidic microenvironment, elevated reactive oxygen species (ROS) levels, and overexpressed specific receptors on the cell surface. According to these unique hallmarks of cancer, stimulus-responsive drug carriers can be designed for targeted anticancer drug delivery and specific drug release in tumor tissues. Herein, a folate-modified pH/ROS dual-responsive polymeric micellar nanosystem was developed for the targeted delivery of doxorubicin (DOX). The drug release profile suggested a sustained drug release from the polymeric micelles and an accelerated drug release at lower pH and higher ROS levels. The cellular uptake assay indicated that the polymeric micelles were internalized by HepG2 cells and that the cellular uptake of micelles can be enhanced by folate modification through a receptor-mediated endocytosis pathway. Furthermore, the folate-modified pH/ROS dual-responsive polymeric micellar nanocarriers demonstrated enhanced inhibition on the migration of HepG2 cells in the cell scratch test and showed improved suppression on the proliferation of HepG2 cells and a lower IC50 than the nonfolate micelles in the cell viability test, indicating the desirable in vitro anticancer efficiency of the nanosystem.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Shuangqing Wang,Yanhong Liu,Xusheng Wang,Liqing Chen,Wei Huang,Tianning Xiong,Nuoya Wang,Jianpeng Guo,Zhonggao Gao,Mingji Jin
Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional preparations often fail to meet multiple demands and provide prompt information about wound status. Here, a pH/ROS dual-responsive hydrogel (OHA-PP@ Z -CA@EGF) was constructed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), chlorogenic acid (CA)-loaded ZIF-8 (Z-CA), and epidermal growth factor (EGF), which possesses intrinsic antibacterial, antioxidant, and angiogenic capacities. Due to the Schiff base and Phenylboronate ester bonds, the hydrogel exhibited excellent mechanical properties, strong adhesion, good biodegradability, high biocompatibility, stable rheological properties, and self-healing ability. Moreover, introducing Z -CA as an initiator and nanofiller led to the additional cross-linking of hydrogel through coordination bonds, which further improved the mechanical properties and antioxidant capabilities. Bleeding models of liver and tail amputations demonstrated rapid hemostatic properties of the hydrogel. Besides, the hydrogel regulated macrophage phenotypes via the NF-κB/JAK-STAT pathways, relieved oxidative stress, promoted cell migration and angiogenesis, and accelerated diabetic wound healing. The hydrogel also enabled real-time monitoring of the wound healing stages by colorimetric detection. This multifunctional hydrogel opens new avenues for the treatment and management of full-thickness diabetic wounds.
研究领域:
材料科学
·
生物医学工程
·
药剂学
·
伤口愈合
·
纳米技术
·
组织工程
✓ 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）