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Mitochondria-targeted alginate/triphenylphosphonium-grafted-chitosan for treatment of hepatocellular carcinoma
RSC Advances ( IF 3.9 ) Pub Date : 2022-08-04 , DOI: 10.1039/d2ra03240f Kholoud K Arafa 1 , Mohamed A Hamzawy 2 , Shaker A Mousa 3 , Ibrahim M El-Sherbiny 1
RSC Advances ( IF 3.9 ) Pub Date : 2022-08-04 , DOI: 10.1039/d2ra03240f Kholoud K Arafa 1 , Mohamed A Hamzawy 2 , Shaker A Mousa 3 , Ibrahim M El-Sherbiny 1
Affiliation
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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. In vitro biological experiments proved that the developed mitotropic NPs exhibited a significantly lower IC50, effectively induced apoptotic cell death and cell cycle arrest. Moreover, the in vivo 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.
中文翻译：
线粒体靶向海藻酸盐/三苯基鏻移植壳聚糖治疗肝细胞癌
抗癌药物的线粒体靶向可以通过不同的机制有效地根除化疗难治性细胞。这项工作提出了线粒体靶向核壳聚合物纳米粒子（NPs）的合理设计，用于将阿霉素（DOX）有效递送至肝癌线粒体。DOX 与海藻酸钠 (SAL) 进行静电纳米复合，然后涂有促有丝分裂的三苯基鏻接枝壳聚糖 (TPP + -g-CS) 纳米壳。聚乙烯醇 (PVA) 共溶于 TPP + -g-CS 溶液中，以增强开发的 NPs 的稳定性。最优的 NPs 公式由 TPP +-g-CS (0.05% w/v) 包覆 DOX-SAL 核心复合物 (0.05% w/v)，相对于 CS (w/w) 具有 0.2% PVA。最佳 NPs 的包封率为 63.33 ± 10.18%；呈球形，粒径为 70-110 nm，表面带正电荷，可增强线粒体的摄取。FTIR 和 DSC 研究结果表明有效的多络合。体外生物学实验证明，所开发的促有丝分裂NPs具有显着降低的IC 50，有效诱导凋亡细胞死亡和细胞周期停滞。此外，体内研究表明，促有丝分裂的 NPs 具有增强的抗肿瘤生物活性以及降低的生物毒性特征。总之，本研究提出了一种有前途的纳米载体系统，可有效地将 DOX 靶向肝肿瘤的线粒体。
更新日期：2022-08-04
中文翻译：
线粒体靶向海藻酸盐/三苯基鏻移植壳聚糖治疗肝细胞癌
抗癌药物的线粒体靶向可以通过不同的机制有效地根除化疗难治性细胞。这项工作提出了线粒体靶向核壳聚合物纳米粒子（NPs）的合理设计，用于将阿霉素（DOX）有效递送至肝癌线粒体。DOX 与海藻酸钠 (SAL) 进行静电纳米复合，然后涂有促有丝分裂的三苯基鏻接枝壳聚糖 (TPP + -g-CS) 纳米壳。聚乙烯醇 (PVA) 共溶于 TPP + -g-CS 溶液中，以增强开发的 NPs 的稳定性。最优的 NPs 公式由 TPP +-g-CS (0.05% w/v) 包覆 DOX-SAL 核心复合物 (0.05% w/v)，相对于 CS (w/w) 具有 0.2% PVA。最佳 NPs 的包封率为 63.33 ± 10.18%；呈球形，粒径为 70-110 nm，表面带正电荷，可增强线粒体的摄取。FTIR 和 DSC 研究结果表明有效的多络合。体外生物学实验证明，所开发的促有丝分裂NPs具有显着降低的IC 50，有效诱导凋亡细胞死亡和细胞周期停滞。此外，体内研究表明，促有丝分裂的 NPs 具有增强的抗肿瘤生物活性以及降低的生物毒性特征。总之，本研究提出了一种有前途的纳米载体系统，可有效地将 DOX 靶向肝肿瘤的线粒体。
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