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用于癌症治疗的辐射诱导控释中敏化剂与脂质体组成的比较研究。

A comparative study of sensitizers and liposome composition in radiation-induced controlled drug release for cancer therapy.

作者信息

Loscertales E, Mateo J, España S

机构信息

Grupo de Física Nuclear, EMFTEL & IPARCOS, Universidad Complutense de Madrid, Madrid, Spain.

Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.

出版信息

J Liposome Res. 2025 Mar;35(1):64-75. doi: 10.1080/08982104.2024.2401800. Epub 2024 Sep 11.

Abstract

This study investigates drug-loaded liposomes designed for controlled release under ionizing radiation to refine cancer treatment precision. Liposomes as carriers enable targeted chemotherapy delivery, reducing healthy tissue damage risk. Liposomes containing poly- or mono-unsaturated fatty acids and various sensitizing agents were assessed for responsiveness to UV light and γ photon irradiation including rose bengal (RB), protoporphyrin IX (PPIX), verteporfin (VP), cercosporin (CERC) and hypericin (HYP). Carboxyfluorescein (CF) was used as a surrogate for drug release measurements. VP and PPIX induced rapid drug release and lipid peroxidation under UV light, while RB prompted quick drug release under UV light and a modest immediate release under γ irradiation, eventually reaching full release a few hours after irradiation, demonstrating dose-dependent effects. Smaller liposomes displayed accelerated release, emphasizing size-dependent kinetics. analyses evaluated radiosensitizing effects of RB-loaded liposomes. Clonogenic assays indicated that RB-filled liposomes had minimal direct radiobiological effects but increased indirect radiation damage, as shown by the curvature of the cell survival curve. Our study sheds light on factors influencing liposomal drug release under ionizing radiation, spotlighting RB as a promising radiosensitizer requiring further investigation for cancer therapy potential.

摘要

本研究调查了用于在电离辐射下实现控释的载药脂质体,以提高癌症治疗的精准度。脂质体作为载体可实现靶向化疗给药,降低对健康组织造成损伤的风险。对含有多不饱和或单不饱和脂肪酸以及各种敏化剂的脂质体进行了评估,以确定其对紫外线和γ光子辐射的反应,这些敏化剂包括孟加拉玫瑰红(RB)、原卟啉IX(PPIX)、维替泊芬(VP)、尾孢菌素(CERC)和金丝桃素(HYP)。使用羧基荧光素(CF)作为药物释放测量的替代物。VP和PPIX在紫外线照射下诱导快速药物释放和脂质过氧化,而RB在紫外线照射下促使药物快速释放,在γ辐射下有适度的即时释放,最终在照射后数小时达到完全释放,显示出剂量依赖性效应。较小的脂质体表现出加速释放,强调了尺寸依赖性动力学。分析评估了载RB脂质体的放射增敏作用。克隆形成试验表明,填充RB的脂质体具有最小的直接放射生物学效应,但增加了间接辐射损伤,如细胞存活曲线的曲率所示。我们的研究揭示了影响电离辐射下脂质体药物释放的因素,突出了RB作为一种有前景的放射增敏剂,其癌症治疗潜力需要进一步研究。

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