JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Quan Wang,Yi Duan,Hongshu Jing,Zhihua Wu,Yu Tian,Ke Gong,Qianqian Guo,Jiali Zhang,Ying Sun,Zhaojun Li,Yourong Duan
Atherosclerosis is a chronic disease initiated by lipid-mediated vascular inflammation . From the perspective of conventional treatment, it is difficult to achieve good therapeutic effects via regulation of a single lipid or anti-inflammatory effects. Herein, we designed an amphiphilic low molecular weight heparin-unsaturated fatty acid conjugate (LMWH-uFA) that acted as both an antiatherosclerotic agent and a nanocarrier with self-delivery properties. Structurally, LMWH-uFA self-assembled to form micelles with LMWH as the shell and uFA as the core, without any additives, which guaranteed their biosafety. Functionally, the hydrophilic segment, LMWH, prevented monocyte adhesion to inhibit early vascular inflammation, and the hydrophobic segment, uFA, could participate in the regulation of blood lipids. The anti-inflammatory drug rapamycin (RAP) was encapsulated in the micellar core, which improved its water solubility, and cooperated with LMWH to achieve targeted blockade of the vascular inflammation cascade at P-selectin. The three treatment modules, LMWH, uFA and RAP, were integrated into one system for different therapeutic targets in anticipation of better efficacy. In an atherosclerosis mouse model, RAP-loaded NPs significantly reduced the plaque area and showed satisfactory curative effects, which were related to the targeting of lipid regulation and inflammation. Thus, these modular micellar nanoparticles offer a promising approach for the clinical treatment of atherosclerosis.
研究领域:
药理学
·
纳米医学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 30
·
IF 11.7
Long Huang,Wei Hu,Long Qun Huang,Qin Xuan Zhou,Zheng Yang Song,Heng Yu Tao,Bing Xu,Can Yang Zhang,Yi Wang,Xin-Hui Xing
Designing highly efficient orally administrated nanotherapeutics with specific inflammatory site–targeting functions in the gastrointestinal tract for ulcerative colitis (UC) management is a noteworthy challenge. Here, we focused on exploring a specific targeting oral nanotherapy, serving as “one stone,” for the directed localization of inflammation and the regulation of redox homeostasis, thereby achieving effects against “two birds” for UC treatment. Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive ε-polylysine nanoparticles at low–molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously. Our results indicate that OPNs@LMWH had high integrin αM–mediated immune cellular uptake efficiency and preferentially accumulated in inflamed tissues. We also confirmed its effectiveness in the treatment experiment of colitis in mice by ameliorating oxidative stress and inhibiting the activation of inflammation-associated signaling pathways while simultaneously bolstering the protective mechanisms of the colonic epithelium. Overall, these findings underscore the compelling dual functionalities of OPNs@LMWH, which enable effective oral delivery to inflamed sites, thereby facilitating precise UC management.
研究领域:
药学
·
纳米技术
·
胃肠病学
·
免疫学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 8
·2172-2188
·
IF 5.831
Haifeng Sun,Dinglingge Cao,Yanhong Liu,Hui Wang,Xue Ke,Tianyuan Ci
Tumor metastasis has become a major obstacle for the clinical treatment of malignant breast cancer. Thus, a delivery system capable of both antitumor and anti-metastasis efficacy is desired. In this work, a low molecular weight heparin (LMWH)-based reduction-sensitive delivery system was developed, aiming to combine the properties of both the antitumor drug and active excipients to achieve a synergistic antitumor and anti-metastatic efficiency as well as resolving the potential adverse effects of both doxorubicin and LMWH. That is, the efficiency of DOX could be enhanced and its toxicity could be lowered. Meanwhile, the biological properties of LMWH could be strengthened and its bleeding risk could also be alleviated. Briefly, drug-loaded crosslinked nanoparticles (DOX/cLLHC2) had a longer blood circulation time and exhibited a rapid reduction-triggered release of DOX. The in vitro assays revealed that DOX/cLLHC2 exhibited a higher cellular uptake and cytotoxicity compared to free DOX. Meanwhile, for the existence of LMWH, DOX/cLLHC2 inhibited cell migration and invasion, as well as effectively inhibited the tube-like formation of human umbilical vein endothelial cells. DOX/cLLHC2 possessed a superior tumor accumulation compared to lipoic acid unmodified nanoparticles and free DOX. Also, DOX/cLLHC2 exhibited encouraging antitumor and anti-metastasis efficiency in an orthotopic breast cancer model. Overall, DOX/cLLHC2 could exert antitumor, anti-metastasis, and anti-angiogenesis efficacy simultaneously as well as having lower systemic toxicity, which makes it suitable for the therapy of metastatic breast carcinoma.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
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）