Zhang Yunjiao, Ma Nan, Luo Congcong, Zhu Jiaquan, Bao Chunrong
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200092 P. R. China
RSC Adv. 2020 Mar 3;10(16):9378-9386. doi: 10.1039/c9ra08926h. eCollection 2020 Mar 2.
Photodynamic therapy (PDT) has the advantages of low toxicity and specificity, but photosensitizers usually fail to accumulate efficiently at the tumor site. In this study, a new multifunctional nano-drug delivery system was exploited by a biomimetic strategy to improve the PDT effects. The self-assembled methoxy poly(ethylene glycol)-poly(lactide--glycolide) (mPEG-PLGA) nanoparticles encapsulated with the photosensitizer chlorin e6 (Ce6) by microfluidics were employed as the nano-core, followed by coating red blood cell (RBC) membranes as the biomimetic agent to prolong the circulation time . In order to boost the therapeutic effect, doxorubicin (Dox) was preloaded into RBC nanovesicles. The cell membrane surface was modified with folic acid (FA) to further enhance the tumor targeting efficiency. The prepared biomimetic nanoparticles with a homogeneous size (70 nm) can trigger sufficient reactive oxygen species (ROS), leading to significant tumor ablation without side effects. In addition, the system had high tumor targeting efficiency, with an increase of 25% compared with no FA-modified nanoparticles. Therefore, this biomimetic multifunctional nanodrug delivery system possesses a prolonged circulation time and higher tumor targeting efficiency and can exert better tumor cytotoxicity for improved PDT due to homophilic targeting .
光动力疗法(PDT)具有低毒性和特异性的优点,但光敏剂通常无法在肿瘤部位有效积累。在本研究中,通过仿生策略开发了一种新型多功能纳米药物递送系统,以提高PDT效果。采用微流控技术将包裹有光敏剂二氢卟吩e6(Ce6)的自组装甲氧基聚(乙二醇)-聚(丙交酯-乙交酯)(mPEG-PLGA)纳米颗粒作为纳米核心,随后包覆红细胞(RBC)膜作为仿生剂以延长循环时间。为了提高治疗效果,将阿霉素(Dox)预先装载到RBC纳米囊泡中。细胞膜表面用叶酸(FA)修饰以进一步提高肿瘤靶向效率。制备的尺寸均匀(70 nm)的仿生纳米颗粒可引发足够的活性氧(ROS),导致显著的肿瘤消融且无副作用。此外,该系统具有较高的肿瘤靶向效率,与未修饰FA的纳米颗粒相比提高了25%。因此,这种仿生多功能纳米药物递送系统具有延长的循环时间和更高的肿瘤靶向效率,并且由于亲同性靶向作用,能够发挥更好的肿瘤细胞毒性以改善PDT效果。