School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
School of Life Science, Jiaying University, Mei Zhou 514015, China.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1704-1719. doi: 10.1021/acsabm.0c01488. Epub 2021 Jan 21.
Black phosphorus (BP) nanosheets with excellent features have been broadly employed for cancer therapy. BPs in blood were known to form BP nanomaterial-corona complexes, yet not explored their biological effects. In this study, BPs as delivery vehicles loaded with doxorubicin (DOX) (BP-DOX) by electrostatic interaction had been successfully prepared for photo-thermal/chemotherapy with a tumor inhibition rate of 81.47% more than the rates of BPs (69.50%) and free DOX (51.91%) in the Hela-bearing mice model by a pH/photo-responsive controlled drug release property. Then, experiments demonstrated that the treatment of healthy mice with BPs led to mild inflammation in the body and oxidative stress in the liver and lung which caused cell apoptosis. studies further showed that oxidative stress and metabolic disorders could be induced by BPs in A549, HepG2, Beas-2B, and LO2 cells. Lastly, the RGD peptide-conjugated red blood cell (RBC) membrane-coated BPs (RGD-RBC@BP) was prepared by lipid insertion and co-ultrasound methods for efficient photo-thermal therapy (PTT) cancer via a tumor-targeted strategy. RGD-RBC@BP showed positive biocompatibility, photo-thermal properties, and increased cellular uptake by Hela cells benefited by the long circulation property of RBC and RGD peptides. Pharmacokinetics and bio-distribution study of RGD-RBC@BP were found to prolong circulation time and tended to accumulate in the tumors, which overexpression of ανβ3 integrin rather than livers after intravenous injection 24 h . After 808 nm laser irradiation, RGD-RBC@BP nanoparticles exhibited a better PTT than PEGylated BPs (BP-PEG). The active-targeting strategy of biomimetic nanomaterials based on the tumor microenvironment have been proved to have favorable biological prospects in cancer PTT.
黑磷（BP）纳米片具有优异的特性，已被广泛应用于癌症治疗。已知 BP 在血液中形成 BP 纳米材料-冠复合物，但尚未探索其生物学效应。在这项研究中，通过静电相互作用，BP 被用作载药载体，装载阿霉素（DOX）（BP-DOX），具有 pH/光响应控制药物释放特性，在荷瘤小鼠模型中，光热/化学治疗的肿瘤抑制率为 81.47%，高于 BP（69.50%）和游离 DOX（51.91%）的抑制率。然后，实验表明，健康小鼠用 BP 处理后，体内会出现轻度炎症，肝脏和肺部会出现氧化应激，导致细胞凋亡。进一步研究表明，BP 可诱导 A549、HepG2、Beas-2B 和 LO2 细胞发生氧化应激和代谢紊乱。最后，通过脂质插入和共超声方法制备了 RGD 肽修饰的红细胞（RBC）膜包覆的 BP（RGD-RBC@BP），通过肿瘤靶向策略，用于高效光热治疗（PTT）癌症。RGD-RBC@BP 表现出良好的生物相容性、光热性能和通过 RBC 和 RGD 肽的长循环特性增加对 Hela 细胞的摄取。RGD-RBC@BP 的药代动力学和生物分布研究发现，其循环时间延长，倾向于在肿瘤中积累，静脉注射 24 h 后，由于 ανβ3 整合素过表达而不是肝脏。在 808nm 激光照射后，RGD-RBC@BP 纳米颗粒的 PTT 效果优于 PEG 化 BP（BP-PEG）。基于肿瘤微环境的仿生纳米材料的主动靶向策略已被证明在癌症 PTT 中具有良好的生物学前景。
