载顺铂介孔聚多巴胺纳米粒子表面包覆 MnO 并被血小板膜所伪装,提供协同抗肿瘤治疗。
Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO and coated with platelet membrane provide synergistic anti-tumor therapy.
机构信息
College of Biological Science and Medical Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, PR China.
UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
出版信息
Int J Pharm. 2024 May 10;656:124093. doi: 10.1016/j.ijpharm.2024.124093. Epub 2024 Apr 6.
A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO NPs were found to have a particle size of approximately 198 nm. MnO is degraded into Mn in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of HO in cells. Mn can catalyze the conversion of HO to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 μg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.
在这项工作中构建了一种多功能纳米平台,旨在改善传统癌症化疗所面临的挑战。顺铂(CP)被负载到介孔聚多巴胺(mPDA)纳米颗粒(NPs)中,载药量为 15.8±0.1%,并使用 MnO 作为孔密封剂。最后,NPs 被血小板膜(PLTM)包裹。PLTM 上的 P-选择素可以与肿瘤细胞膜上高度表达的 CD44 结合,从而提高 NPs 的靶向性能。此外,PLTM 上的 CD47 可以防止 NPs 被巨噬细胞吞噬,有利于免疫逃逸。最终的 PLTM-CP@mPDA/MnO NPs 的粒径约为 198nm。MnO 在肿瘤微环境中降解为 Mn,导致 mPDA 中的孔中 CP 释放。CP 既是化疗药物,又可以增加细胞中 HO 的浓度。Mn 可以催化 HO 转化为 OH,导致氧化损伤和化学动力学治疗。此外,Mn 可以用作磁共振成像(MRI)的造影剂。进行了体外和体内实验以探索 NPs 的治疗效果。当 CP 的浓度为 30μg/mL 时,NPs 导致约 50%的细胞死亡。结果发现,PLTM-CP@mPDA/MnO NPs 靶向癌细胞,并在肿瘤部位引起广泛的细胞凋亡。从而抑制肿瘤生长。没有观察到负的非靶向副作用。MRI 可用于确认肿瘤部位存在 NPs。总的来说,这里开发的纳米平台提供了协同化疗和化学动力学治疗,并且可以潜在地用于通过 MRI 监测的有效癌症治疗。