Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence Imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity
Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence Imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity
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DOI：
10.1021/la0607499
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发表时间：
2006-09-12
期刊：
影响因子：
3.9
通讯作者：
Lal, Ratnesh
中科院分区：
文献类型：
--
作者：
Ramachandran, Srinivasan;Quist, Arjan P.;Lal, Ratnesh
顺铂是对抗许多癌症的最有效的细胞毒性剂。然而，由于靶细胞的低效摄取，其使用受到限制。据报道，顺铂的脂质体制剂部分克服了这一限制。脂质体-顺铂制剂的物理化学特征，包括其大小、稳定性、包封效率和细胞质内化效率，在有效使用脂质体制剂中起重要作用。我们使用原子力显微镜（AFM），以确定顺铂封装的脂质体的物理化学特性，原子力显微镜和荧光显微镜，以检查其细胞质的内化，和活/死试验，以检查其细胞毒性。未包封的顺铂是球形的，大小为10 - 50 nm。AFM力解剖和刚度测量表明，顺铂封装的脂质体是显着更硬（类似于100%），更稳定的脂质体没有封装顺铂。直径接近250 nm的顺铂包封脂质体（纳米脂质体）最有效地内化，并以时间依赖性方式诱导细胞毒性。类似尺寸的不含顺铂的脂质体，尽管内化在细胞质中，但不诱导细胞毒性。
Cisplatin is the most effective cytotoxic agent against many cancers. Its usage, however, is limited due to inefficient uptake by the target cells. A liposomal formulation of cisplatin is reported to partly overcome this limitation. Physicochemical characteristics of the liposome-cisplatin preparation, including its size, stability, encapsulation efficiency, and cytoplasmic internalization efficiency, play a significant role in an effective usage of liposomal formulations. We have used atomic force microscopy (AFM) to determine physicochemical characteristics of cisplatin-encapsulated liposomes, AFM and fluorescence microscopy to examine their cytoplasmic internalization, and Live/ Dead assay to examine their cell toxicity. Nonencapsulated cisplatin is globular and 10-50 nm in size. AFM force-dissection and stiffness measurements show that cisplatin-encapsulated liposomes are significantly stiffer (similar to 100%) and more stable than liposomes without encapsulated cisplatin. Cisplatin-encapsulated liposomes of similar to 250 nm diameter (nanoliposomes) are most efficiently internalized and induce cell toxicity in a time-dependent manner. Liposomes without cisplatin of similar dimensions, although internalized in the cell cytoplasm, do not induce cell toxicity.