Sorafenib/2800Z Co-Loaded into Cholesterol and PEG Grafted Polylysine NPs for Liver Cancer Treatment.
Sorafenib/2800Z Co-Loaded into Cholesterol and PEG Grafted Polylysine NPs for Liver Cancer Treatment.
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DOI：
10.3390/ph16010119
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发表时间：
2023-01-13
期刊：
影响因子：
--
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Zhang C;Zhong W;Cao Y;Liu B;Tao X;Li Z
由于晚期癌症对治疗方案的反应性较低，肝癌的治疗仍然具有挑战性。索拉非尼是治疗晚期肝癌的一线化疗药物，但经常会出现严重的副作用，导致停止化疗。我们之前开发了一种特异性的SIRT7抑制剂2800Z，它可以抑制肿瘤生长，并增强索拉非尼的化疗敏感性。在本研究中，我们构建了胆固醇和谷胱甘肽敏感的聚乙二醇化修饰的聚赖氨酸聚合物纳米粒(MPssPC)来负载索拉非尼(SOR)和SIRT7抑制剂2800Z，形成双负载纳米粒(S2@PsPC)，以降低索拉非尼的毒性，提高其对肝癌的疗效。S2@PSPC纳米粒子的平均尺寸约为370 nm，Zeta电位约为50-53 mV。我们发现，药物的释放具有pH敏感性，并且在模拟肿瘤环境的酸释放介质中显著加速。此外，S2@PSPC纳米粒在体外对肝癌细胞具有抑制增殖和诱导凋亡的作用。体内研究进一步表明，S2@PsPC对肝癌具有高度的特异性，但对包括心脏、肾脏、肺和肝脏在内的主要器官的亲和力和毒性较低。因此，我们的数据进一步证实了SIRT7抑制剂和索拉非尼联合用于肝癌的治疗，并为靶向治疗提供了新的药物输送系统。
The treatment of liver cancer remains challenging due to the low responsiveness of advanced cancer to therapeutic options. Sorafenib is the first line chemotherapeutic drug for advanced liver cancer but is frequently associated with severe side effects lead to discontinuation of chemotherapy. We previously developed a specific SIRT7 inhibitor 2800Z, which suppressed tumor growth and enhanced the chemosensitivity of sorafenib. In this study, we constructed polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z to form dual-loaded NPs (S2@PsPCs) to reduce the toxicity and increase efficacy of sorafenib in liver cancer. The average size of S2@PsPC NPs was approximately 370 nm and the zeta potential was approximately 50–53 mV. We found that the release of the drugs exhibited pH sensitivity and was significantly accelerated in an acid release medium simulating the tumor environment. In addition, S2@PsPC NPs inhibited the proliferation and induced apoptosis of liver cancer cells in vitro. An in vivo study further revealed that S2@PsPCs showed high specificity to the liver cancer but low affinity and toxicity to the main organs including the heart, kidneys, lungs, and liver. Our data thus further approved the combination of a SIRT7 inhibitor and sorafenib for the treatment of liver cancer and provided new drug delivery system for targeted therapy.
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影响因子：
6.2
作者：
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13.5
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