Versatile hyaluronic acid modified AQ4N-Cu(II)-gossypol infinite coordination polymer nanoparticles: Multiple tumor targeting, highly efficient synergistic chemotherapy, and real-time self-monitoring. (February 2018)

• Record Type: Journal Article
• Authors: Shen, Shihong; Wu, Youshen; Li, Ke; Wang, Ya; Wu, Jimin; Zeng, Yun; Wu, Daocheng
• Is Part Of: Biomaterials. Volume 154(2018)
• Page Start: 197
• Page End: 212
• Publication Date: 2018-02
• Subjects: Infinite coordination polymer nanoparticles -- Synergistic chemotherapy -- Multiple tumor targeting -- Real-time self-monitoring; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2017.11.001
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: A novel strategy for the preparation of infinite coordination polymer nanoparticles (ICPs) based nanomedicines was developed, with which hyaluronic acid modified AQ4N-Cu(II)-gossypol nanoparticles (HA@AQ4N-Cu(II)-gossypol NPs) were obtained. This is a highly efficient nanomedicine, in which gossypol serves as a chemotherapeutic agent and a self-carrier material; Cu(II) serves as the connecting point and anti-tumor enhancer; AQ4N not only serves as a chemotherapeutic agent and self-carrier material, but also as the self-monitor based on its inherent fluorescence. HA@AQ4N-Cu(II)-gossypol NPs possessed a spherical shape with a dynamic size of 88.7 ± 7.4 nm, and the total drug-loading content and drug encapsulation efficiency are 77.41% and 100%, respectively. This nanomedicine has a multiple tumor-targeting ability caused by HA-receptor mediation and pH-responsive drug release. A significantly low combination index (0.097) of AQ4N and gossypol is ascertained. In vivo experiments indicate that it accumulates and significantly releases drugs at the tumor region. With the use of only one-fiftieth of AQ4N and half of gossypol of the generally administered dose, they can achieve significantly high anti-tumor efficiency with negligible side effects. Importantly, the switching-type changed fluorescence of AQ4N can be used for in vivo real-time self-monitoring of the drug release and distribution, which allows us to adjust the administration dose and time for different tumor types and stages for individual therapy. Graphical abstract: A versatile highly efficient nanomedicine of HA@AQ4N-Cu(II)-gossypol NPs is developed, in which two low toxicity anticancer drugs, AQ4N and gossypol, co-coordinating with Cu(II) to form AQ4N-Cu(II)-gossypol ICPs, and then hyaluronic acid is modified on their surface. This nanomedicine has the characteristics of multiple tumor targeting, highly efficient cancer synergistic chemotherapy, and real-time self-monitoring of drug release and distributions in vivo .