pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment.
pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment.
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DOI：
10.1016/j.biopha.2021.112317
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发表时间：
2021-12
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影响因子：
--
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伊立替康(Irinotecan，IRN)是喜树碱的半合成衍生物，具有拓扑异构酶I抑制剂的作用。IRN在世界范围内被用于治疗几种类型的癌症，包括结直肠癌，但它的使用可能会导致严重的不良反应，如腹泻和骨髓抑制。脂质体被广泛用作药物输送系统，可以提高化疗活性，减少副作用。脂质体也可以是pH敏感的，在酸性环境中优先释放其内容物，如肿瘤，并为靶向目的而表面功能化。在此，我们开发了一种叶酸包裹的pH敏感脂质体，作为IRN的药物输送系统，以达到改善肿瘤治疗的目的，而没有潜在的不良反应。制备了含有IRN的脂质体，并对其粒径、多分散性指数、Zeta电位、浓度、包封率、细胞摄取和释放曲线进行了表征。用小鼠结直肠癌模型观察其抗肿瘤活性，并通过血液学/生化试验和主要脏器的组织学分析评价其毒性。结果表明，微囊尺寸小于200 nm，分散性小，表面电荷接近中性，包封率高达90%以上。该系统具有较高的细胞内释药能力，具有较长的缓释和pH依赖性。重要的是，叶酸包被的pH敏感制剂比单独的pH依赖体系或游离药物具有显著更好的抗肿瘤活性。含IrN组肿瘤组织呈大面积坏死。此外，对于被调查的组，没有发现全身毒性的证据。因此，我们开发的纳米片Irn递送系统可能成为传统结直肠癌治疗的替代方案。
Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment.
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影响因子：
8
作者：
Casadó A;Sagristá ML;Mora M
通讯作者：
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影响因子：
7.5
作者：
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Oliveira, Monica Cristina
DOI：
10.1073/pnas.0800835105
发表时间：
2008-08-12
影响因子：
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影响因子：
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