Newly Designed Silica-Containing Redox Nanoparticles for Oral Delivery of Novel TOP2 Catalytic Inhibitor for Treating Colon Cancer
Newly Designed Silica-Containing Redox Nanoparticles for Oral Delivery of Novel TOP2 Catalytic Inhibitor for Treating Colon Cancer
复制标题
新设计的含二氧化硅氧化还原纳米颗粒用于口服治疗结肠癌的新型 TOP2 催化抑制剂
DOI：
10.1002/adhm.201700428
复制
发表时间：
2017
影响因子：
10
通讯作者：
Nagasaki Yukio
中科院分区：
文献类型：
--
作者：
Vong Long Binh;Kimura Shinya;Nagasaki Yukio
尽管口服药物递送是最常见的药物施用途径，但常规聚合物纳米载体在胃肠（GI）环境中表现出低药物负载能力和低稳定性。在这项研究中，开发了一种新设计的具有活性氧（ROS）清除能力的含二氧化硅氧化还原纳米颗粒（siRNP），作为新型疏水抗癌化合物BNS-22的理想口服纳米载体，用于治疗体内结肠炎相关结肠癌。与常规氧化还原纳米颗粒相比，二氧化硅部分的交联显著增强了在酸性条件下的稳定性，并提高了siRNP的BNS-22负载能力。小鼠口服BNS-22-负载siRNP（BNS-22@siRNP）后，显著提高了BNS-22的生物利用度和结肠肿瘤分布。因此，与其他对照治疗相比，BNS-22@siRNP显著抑制结肠炎相关结肠癌小鼠的肿瘤进展。值得注意的是，口服给药后未观察到siRNP载体的全身吸收。有趣的是，口服给予BNS-22@siRNP由于其ROS清除能力而显著抑制了BNS-22的不良作用，并且在用BNS-22@siRNP治疗的小鼠中没有观察到其他明显的毒性，尽管siRNP位于胃肠道中。我们的研究结果表明，siRNP是一个有前途的口服药物纳米载体的癌症治疗。
Although oral drug delivery is the most common route of drug administration, the conventional polymeric nanocarriers exhibit a low drug loading capacity and low stability in the gastrointestinal (GI) environments. In this study, a newly designed silica‐containing redox nanoparticle (siRNP) with reactive oxygen species (ROS) scavenging capacity is developed as an ideal oral nanocarrier for a novel hydrophobic anticancer compound BNS‐22 to treat colitis‐associated colon cancer in vivo. Crosslinking of silica moieties significantly enhances the stability under acidic conditions and improves BNS‐22 loading capacity of siRNP compared to the conventional redox nanoparticle. After oral administration to mice, BNS‐22‐loaded siRNP (BNS‐22@siRNP) remarkably improves bioavailability and colonic tumor distribution of BNS‐22. As the result, BNS‐22@siRNP significantly inhibits the tumor progression in colitis‐associated colon cancer mice compared to other control treatments. It is noteworthy that no systemic absorption of siRNP carrier is observed after oral administration. Interestingly, orally administered BNS‐22@siRNP significantly suppresses the adverse effects of BNS‐22 owing to its ROS scavenging capacity, and no other noticeable toxicities are observed in mice treated with BNS‐22@siRNP although siRNP is localized in the GI tract. Our results indicate that siRNP is a promising oral drug nanocarrier for cancer therapy.