School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Zhangjiang Hi-Tech Park, Pudong New District, Shanghai, 201203, P R China.
Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
J Nanobiotechnology. 2023 Jul 4;21(1):206. doi: 10.1186/s12951-023-01949-5.
Enterocyte uptake with high binding efficiency and minor endogenous interference remains a challenge in oral nanocarrier delivery. Enterocyte membrane-biomimetic lipids may universally cooperate with endogenous phosphatidyl choline via a biorthogonal group. In this study, we developed a sophorolipid-associated membrane-biomimetic choline phosphate-poly(lactic-co-glycolic) acid hybrid nanoparticle (SDPN). Aided by physical stability in the gastrointestinal tract and rapid mucus diffusion provided by association with sophorolipid, these nanoparticles show improved endocytosis, driven by dipalmitoyl choline phosphate-phosphatidyl choline interaction as well as its optimized membrane fluidity and rigidity. Luteolin- and silibinin-co-loaded with SDPN alleviated breast cancer metastasis in 4T1 tumor-bearing mice by regulating the conversion of tumor-associated M2 macrophages into the M1 phenotype and reducing the proportion of the M2-phenotype through co-action on STAT3 and HIF-1α. In addition, SDPN reduces angiogenesis and regulates the matrix barrier in the tumor microenvironment. In conclusion, this membrane-biomimetic strategy is promising for improving the enterocyte uptake of oral SDPN and shows potential to alleviate breast cancer metastasis.
肠细胞摄取具有高结合效率和较小的内源性干扰仍然是口服纳米载体递送的一个挑战。肠细胞膜仿生脂质可能通过生物正交基团与内源性磷脂酰胆碱普遍合作。在本研究中，我们开发了一种神经鞘氨醇相关的细胞膜仿生胆碱磷酸-聚（乳酸-共-乙醇酸）混合纳米粒子（SDPN）。通过与神经鞘氨醇结合提供的胃肠道内的物理稳定性和快速黏液扩散，这些纳米粒子显示出改善的内吞作用，由二棕榈酰胆碱磷酸-磷脂酰胆碱相互作用以及其优化的膜流动性和刚性驱动。通过调节与肿瘤相关的 M2 巨噬细胞向 M1 表型的转化以及通过对 STAT3 和 HIF-1α 的共同作用降低 M2 表型的比例，载有木犀草素和水飞蓟宾的 SDPN 减轻了 4T1 荷瘤小鼠的乳腺癌转移。此外，SDPN 减少了血管生成并调节了肿瘤微环境中的基质屏障。总之，这种细胞膜仿生策略有望改善口服 SDPN 的肠细胞摄取，并显示出减轻乳腺癌转移的潜力。
