Arafa Kholoud K, Hamzawy Mohamed A, Mousa Shaker A, El-Sherbiny Ibrahim M
Nanomedicine Research Labs, Center for Materials Science (CMS), Zewail City of Science and Technology Ahmed Zewail Road, October Gardens, 6th of October City 12578 Giza Egypt
Pharmacology & Toxicology Department, Faculty of Pharmacy, Fayoum University Fayoum Egypt.
RSC Adv. 2022 Aug 4;12(34):21690-21703. doi: 10.1039/d2ra03240f.
Mitochondrial targeting of anticancer drugs can effectively eradicate chemotherapy-refractory cells through different mechanisms. This work presents the rational designing of mitochondria-targeted core-shell polymeric nanoparticles (NPs) for efficient delivery of doxorubicin (DOX) to the hepatic carcinoma mitochondria. DOX was electrostatically nano-complexed with sodium alginate (SAL) then coated with mitotropic triphenylphosphonium-grafted chitosan (TPP-g-CS) nanoshell. Polyvinyl alcohol (PVA) was co-solubilized into the TPP-g-CS solution to enhance the stability of the developed NPs. The optimum NPs formula is composed of TPP-g-CS (0.05% w/v) coating a DOX-SAL core complex (0.05% w/v), with 0.2% PVA relative to CS (w/w). The optimum NPs attained an entrapment efficiency of 63.33 ± 10.18%; exhibited a spherical shape with particle size of 70-110 nm and a positive surface charge which enhances mitochondrial uptake. FTIR and DSC studies results were indicative of an efficacious poly-complexation. biological experiments proved that the developed mitotropic NPs exhibited a significantly lower IC, effectively induced apoptotic cell death and cell cycle arrest. Moreover, the studies demonstrated an enhanced antitumor bioactivity for the mitotropic NPs along with a reduced biological toxicity profile. In conclusion, this study proposes a promising nanocarrier system for the efficient targeting of DOX to the mitochondria of hepatic tumors.
将抗癌药物靶向线粒体可通过不同机制有效根除化疗难治性细胞。本研究提出了一种线粒体靶向核壳聚合物纳米颗粒（NPs）的合理设计方案，用于将阿霉素（DOX）高效递送至肝癌细胞的线粒体。DOX与海藻酸钠（SAL）通过静电作用形成纳米复合物，然后用促线粒体的三苯基膦接枝壳聚糖（TPP-g-CS）纳米壳包覆。将聚乙烯醇（PVA）共溶解到TPP-g-CS溶液中，以提高所制备纳米颗粒的稳定性。最佳纳米颗粒配方由包覆DOX-SAL核复合物（0.05% w/v）的TPP-g-CS（0.05% w/v）组成，相对于壳聚糖（w/w）含有0.2%的PVA。最佳纳米颗粒的包封率达到63.33±10.18%；呈现球形，粒径为70-110nm，表面带正电荷，可增强线粒体摄取。傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）研究结果表明形成了有效的多聚复合物。生物学实验证明，所制备的促线粒体纳米颗粒表现出显著更低的半数抑制浓度（IC），有效诱导细胞凋亡和细胞周期阻滞。此外，研究表明促线粒体纳米颗粒具有增强的抗肿瘤生物活性以及降低的生物毒性。总之，本研究提出了一种有前景的纳米载体系统，可将DOX高效靶向至肝肿瘤的线粒体。
