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脂质体递送有机硒-顺铂复合物作为治疗结肠癌的新方法。

Liposomal delivery of organoselenium-cisplatin complex as a novel therapeutic approach for colon cancer therapy.

机构信息

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Colloids Surf B Biointerfaces. 2024 Oct;242:114085. doi: 10.1016/j.colsurfb.2024.114085. Epub 2024 Jul 10.

Abstract

Cisplatin is a widely-used chemotherapeutic agent for the treatment of various solid neoplasms including colon cancer. Cisplatin-induced DNA damage is restricted due to dose-related adverse reactions as well as primary resistance mechanisms. Therefore, it is imperative to utilize novel therapeutic approaches to circumvent cisplatin limitations and attenuate its normal tissues toxicity. In this study, we exploited a novel PEGylated liposomes with greater efficiency to treat colon cancer. For this, an organoselenium compound (diselanediylbis decanoic acid (DDA)) was synthesized, and liposomes composed of Egg PC or HSPC, as well as DOPE, mPEG-DSPE, cholesterol and DDA at varying molar ratios were prepared by using thin-film method. Cisplatin loading was performed through incubation with liposomes. Characterization of nanoliposomes indicated a favarable size range of 91-122 nm and negative zeta potential of -9 to -22 mv. The organoselenium compound significantly improved cisplatin loading efficiency within the liposomes (83.4 %). Results also revealed an efficient bioactivity of cisplatin liposome on C26 cells compared to the normal cells. Further, DDA bearing liposomes significantly improved drug residence time in circulation, reduced toxicity associated with the normal tissues, and enhanced drug accumulation within the oxidative tumor microenvironment. Collectively, results indicated that cisplatin encasement within liposomes by using this method could significantly improve the therapeutic efficacy in vivo, and merits further investigations.

摘要

顺铂是一种广泛应用于治疗各种实体肿瘤的化疗药物,包括结肠癌。由于剂量相关的不良反应和原发性耐药机制,顺铂诱导的 DNA 损伤受到限制。因此,利用新的治疗方法来规避顺铂的局限性并减轻其对正常组织的毒性至关重要。在本研究中,我们利用一种新型的聚乙二醇化脂质体来更有效地治疗结肠癌。为此,合成了一种有机硒化合物(二硒代二癸酸(DDA)),并通过薄膜法制备了由 Egg PC 或 HSPC 以及 DOPE、mPEG-DSPE、胆固醇和 DDA 组成的脂质体,其摩尔比不同。通过与脂质体孵育来进行顺铂载药。纳米脂质体的特性分析表明,其粒径范围为 91-122nm,zeta 电位为-9 至-22mv。有机硒化合物显著提高了脂质体内部的顺铂载药效率(83.4%)。结果还表明,与正常细胞相比,载顺铂脂质体对 C26 细胞具有更高的生物活性。此外,载有 DDA 的脂质体能够显著延长药物在循环中的停留时间,降低与正常组织相关的毒性,并增强药物在氧化肿瘤微环境中的积累。综上所述,结果表明,通过这种方法将顺铂包裹在脂质体中可以显著提高体内的治疗效果,值得进一步研究。

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