School of Pharmacy , Shenyang Pharmaceutical University , Shenyang 110016 , China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 , China.
ACS Appl Mater Interfaces. 2019 Dec 18;11(50):46614-46625. doi: 10.1021/acsami.9b18388. Epub 2019 Dec 5.
Cell membrane-coated nanocarriers have been developed for drug delivery due to their enhanced blood circulation and tissue targeting capacities; however, previous works have generally focused on spherical nanoparticles and extracellular barriers. Many living organisms with different shapes, such as rod-shaped bacilli and rhabdovirus, display different functionalities regarding tissue penetration, cellular uptake, and intracellular distribution. Herein, we developed cancer cell membrane (CCM)-coated nanoparticles with spherical and rod shapes. CCM-coated nanorods (CRs) showed superior endocytosis efficiency compared with their spherical counterparts (CCM-coated nanospheres, CSs) due to the caveolin-mediated pathway. Moreover, CRs can effectively accumulate in the endoplasmic reticulum (ER) region and ship the loaded DOX to the nucleus at a considerable concentration, resulting in ER stress and subsequent apoptosis. After intravenous injection into human pancreatic adenocarcinoma cell (BxPC-3) and pancreatic stellate cell (HPSC) hybrid tumor-bearing nude mice, CRs exhibited improved immune escape ability, rapid extracellular matrix (ECM) penetration (8.2-fold higher than CSs), and enhanced tumor accumulation, further contributing to the enhanced antitumor efficacy. These findings may actually suggest the significance of shape design in improving current cell membrane-based drug delivery systems for effective subcellular targets and tumor therapy.
细胞膜包覆的纳米载体由于其增强的血液循环和组织靶向能力而被开发用于药物递送; 然而，以前的工作通常集中在球形纳米粒子和细胞外屏障上。许多具有不同形状的生物体，如棒状杆菌和弹状病毒，在组织穿透、细胞摄取和细胞内分布方面表现出不同的功能。在此，我们开发了具有球形和棒形的癌细胞膜 (CCM) 包覆的纳米粒子。由于 caveolin 介导的途径，CCM 包覆的纳米棒 (CRs) 表现出比其球形对应物 (CCM 包覆的纳米球，CSs) 更高的内吞效率。此外，CRs 可以有效地在粗面内质网 (ER) 区域积累，并将负载的 DOX 以相当高的浓度运送到细胞核，导致 ER 应激和随后的细胞凋亡。在静脉注射到人胰腺腺癌细胞 (BxPC-3) 和胰腺星状细胞 (HPSC) 杂交肿瘤荷瘤裸鼠后，CRs 表现出增强的免疫逃逸能力、快速的细胞外基质 (ECM) 穿透 (比 CSs 高 8.2 倍) 和增强的肿瘤积累，进一步增强了抗肿瘤疗效。这些发现实际上可能表明形状设计在改善当前基于细胞膜的药物递送系统以实现有效亚细胞靶标和肿瘤治疗方面的重要性。
