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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2019 ·Vol. 108 ·期 1 ·148-156 · IF 3.221

Acid-sensitive ROS-triggered dextran-based drug delivery system for advanced chemo-photodynamic synergistic therapy

Yanli Bao,Liping Yin,Lin Liu,Li Chen

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.

研究领域: 药学 · 肿瘤学 · 生物医学工程
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Natural Product Communications · 2022 · IF 1.496

Poly (Thioether-Polyesters) Micelles Encapsulation Induces ROS-Triggered Targeted Release of Tangeretin

Bozhan Tan,Zhiwen Qi,Guliang Yang,Haiyan Zhong

Tangeretin (Tan) possesses great anti-oxidation and anti-inflammation bioactivities; however, it is accompanied by poor water solubility, which leads to inefficient cellular internalization. To address this issue, a reactive oxygen species (ROS)-triggered poly (thioether-polyesters) micelle (PDHP, PEG-DTT) was designed and prepared via self-assembly, which consisted of poly (thioether-polyesters) as the hydrophilic shell, and the drug Tan as the hydrophobic inner core. The micelles (Tan@ PDHP), with a 63.15% loading efficiency of Tan, showed negligible cytotoxicity, high stability in phosphate-buffered saline buffer (pH  =  7.4), and continuous release of Tan with the stimulation of H2O2. In addition, this Tan loading micelle was more efficient in responding to the formation of ROS in the lipopolysaccharide-stimulated RAW264.7 cells compared to that of the free Tan. In short, the strategy of encapsulating the low solubility Tan in ROS-triggered poly (thioether-polyesters) micelles provides an effective assay of enhancing Tan's antioxidative activity.

CAS / MDL: 3483-12-3
研究领域: 药学 · 纳米技术 · 药物递送系统 · 生物医学工程
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

ROS-Triggered Self-Assembled Nanoparticles Based on a Chemo-Sonodynamic Combinational Therapy Strategy for the Noninvasive Elimination of Hypoxic Tumors

Yibing Li,Ling Lin,Jiashan Xie,Lixue Wei,Shuping Xiong,Kunyi Yu,Bingchen Zhang,Shengtao Wang,Zibo Li,Yan Tang,Guimei Chen,Zhongjun Li,Zhiqiang Yu,Xuefeng Wang

The hypopermeability and hypoxia in the tumor milieu are important factors that limit multiple treatments. Herein, the reactive oxygen species (ROS)-triggered self-assembled nanoparticles (RP-NPs) was constructed. The natural small molecule Rhein (Rh) was encapsulated into RP-NPs as a sonosensitizer highly accumulated at the tumor site. Then highly tissue-permeable ultrasound (US) irradiation induced apoptosis of tumor cells through the excitation of Rh and acoustic cavitation, which prompted the rapid production of large amounts of ROS in the hypoxic tumor microenvironment. In addition, the thioketal bond structures in the innovatively designed prodrug LA-GEM were triggered and broken by ROS to achieve rapid targeted release of the gemcitabine (GEM). Sonodynamic therapy (SDT) increased the tissue permeability of solid tumors and actively disrupted redox homeostasis via mitochondrial pathways to kill hypoxic tumor cells, and the triggered response mechanism to GEM synergistically amplified the effect of chemotherapy. The chemo-sonodynamic combinational treatment approach is highly effective and noninvasive, with promising applications for hypoxic tumor elimination, such as in cervical cancer (CCa) patients who want to maintain their reproductive function.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 药学 · 肿瘤学
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JOURNAL OF CONTROLLED RELEASE · 2022 · IF 11.467

ROS-triggered nanoinducer based on dermatan sulfate enhances immunogenic cell death in melanoma

Qixiong Zhang,Shanshan Li,Jiandong Ren,Xia He,Houkui Shi,Fuzhong Zhang,Hui Li,Rongsheng Tong

Due to its complexity, diversity and heterogeneity, melanoma is a kind of malignant tumor. It has been proved that the enhancement of anti-tumor immune response such as immunogenic cell death (ICD) is an important therapeutic strategy. In previous studies, we confirmed that dermatan sulfate (DS) from skin tissue could specifically homing to melanoma B16F10 cells. In this study, we propose a nanoinducer (DOX/ADS NP) based on a functional DS for melanoma. This nanosystem is composed of DS as framework, aromatic thioketal derivative (ATK) as functional grafting unit and doxorubicin (DOX) designed as an ICD inducer. Through the intermolecular interaction between DOX and ATK, DOX/ADS NP with specific-homing, high-loading and ROS-triggering release was obtained via self-assemble. Compared with free DOX and non-functionalized nanomedicine , DOX/ADS NP could release DOX into B16F10 cells better, and strongly induce the translocation of calreticulin (CRT) to the cell membrane . CRT is a marker of ICD, also as a “eat me” signal to stimulate the maturation and antigen presentation of dendritic cells. Therefore, a series of subsequent immune responses were activated: maturation of dendritic cells, T cells proliferation, increased tumor-infiltrating CTLs and the ratio of CTLs to Tregs, and up-regulated cytotoxic cytokine expression. In conclusion, DOX/ADS NP promoted ICD-associated immune response through more specific targeting effect and sensitive responsive DOX release, achieving better inhibitory effect on melanoma than free DOX and other nanoformulation. This biomimetic ICD nanoinducer based on DS is expected to provide new strategies and references for the treatment of melanoma.

研究领域: 肿瘤学 · 免疫疗法 · 纳米技术 · 药学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Anti-fouling coating with ROS-Triggered On-Demand regulation of inflammation to favor tissue healing on vascular devices

Hui Yan,Lietao Wang,Haoshuang Wu,Yongqi An,Yumei Qin,Zhen Xiang,Huining Wan,Yanfei Tan,Li Yang,Fanjun Zhang,Qing Jiang,Rifang Luo,Yunbing Wang

Unhealthy vascular tissue healing after stenting is primarily triggered by endothelial dysfunction and excessive smooth muscle cell proliferation, which is induced and aggravated by local thrombosis and excessive inflammation. Excessive inflammatory response is closely related to elevated concentrations of reactive oxygen species (ROS). Here, an environment-friendly coating strategy termed “Anti-fouling plus” with inflammatory self-regulation ability was proposed. Upon this, membrane-mimicking copolymer MA(PCLA) served as the antifouling coating, effectively inhibiting coagulation and inflammation during the early stage of implantation. Furthermore, a ROS-responsive prodrug was drawn into the coating to promote tissue healing. A molecular prodrug of thioketal-bearing dexamethasone was engineered to be released in a controlled and responsive manner in response to externally high levels of ROS. The released dexamethasone exhibited highly effective anti-inflammation properties after implantation. The combination of ROS-responsive prodrug and membrane-mimicking antifouling interface strategy intelligently integrated inflammation responsiveness and regulation, which could mediate a gentle vascular microenvironment and thus promote vascular remodeling. In vivo stent implantation studies demonstrated that the proposed “Anti-fouling plus” coating effectively inhibited neointima hyperplasia, modulated the inflammatory response and promoted endothelialization, offering promising surface modification approaches for vascular stents.

研究领域: 生物材料 · 组织工程 · 血管生物学 · 药物递送系统
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