Zhang Ziqi, Lu Zhuanning, Yuan Qiong, Zhang Chen, Tang Yanli
Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, P. R. China.
J Mater Chem B. 2021 Mar 11;9(9):2240-2248. doi: 10.1039/d0tb02996c.
Stimuli-responsive and active targeted drug release is highly significant and challenging for precise and effective cancer therapy. Herein, a reactive oxygen species (ROS)-responsive drug delivery system iRGD-BDOX@CPNs with active targeting for chemo-/photodynamic (PDT) synergistic therapy has been reported. This nanocarrier iRGD-BDOX@CPNs is constructed by the self-assembly of conjugated polymer poly(fluorene-co-vinylene) (PFV), prodrug BDOX (doxorubicin modified with a phenylboronic acid ester group) and an amphiphilic polymer (DSPE-PEG) modified with internalized RGD (DSPE-PEG-iRGD). The hydrophobic inner cores formed by PFV main chains tightly enclose BDOX. Due to PFV generating many ROS by light triggering, the BDOX prodrug can be in situ activated, resulting in the highly efficient drug release. In addition, the remarkable fluorescence recovery could be used for real-time monitoring of drug delivery and guiding antitumor therapy. Contributing to the specific recognition between iRGD and integrin αvβ3 receptors over-expressed on the surface of tumor cells, the active targeting and uptake of iRGD-BDOX@CPNs in tumor cells are greatly enhanced. The prominent anti-cancer effect of iRGD-BDOX@CPNs is realized by targeted drug delivery and synergistic therapeutic effects of PDT/chemotherapy. This study illustrates that the development of ROS-responsive and targeted drug delivery nanocarriers iRGD-BDOX@CPNs provides a new insight for controllable drug release and tumor precision therapy.
刺激响应性和主动靶向药物释放对于精确有效的癌症治疗具有高度的重要性和挑战性。在此，报道了一种具有活性靶向用于化疗/光动力（PDT）协同治疗的活性氧（ROS）响应性药物递送系统iRGD-BDOX@CPNs。这种纳米载体iRGD-BDOX@CPNs由共轭聚合物聚（芴-共-亚乙烯基）（PFV）、前药BDOX（用苯基硼酸酯基团修饰的阿霉素）和用内化RGD修饰的两亲性聚合物（DSPE-PEG）（DSPE-PEG-iRGD）自组装而成。PFV主链形成的疏水内核紧密包裹着BDOX。由于PFV通过光触发产生大量ROS，BDOX前药可被原位激活，从而实现高效的药物释放。此外，显著的荧光恢复可用于实时监测药物递送并指导抗肿瘤治疗。由于iRGD与肿瘤细胞表面过度表达的整合素αvβ3受体之间的特异性识别，iRGD-BDOX@CPNs在肿瘤细胞中的主动靶向和摄取大大增强。iRGD-BDOX@CPNs突出的抗癌效果是通过靶向药物递送以及PDT/化疗的协同治疗作用实现的。这项研究表明，ROS响应性和靶向药物递送纳米载体iRGD-BDOX@CPNs的开发为可控药物释放和肿瘤精准治疗提供了新的见解。
