Ramachandran Srinivasan, Quist Arjan P, Kumar Sashi, Lal Ratnesh
Neuroscience Research Institute, University of California at Santa Barbara, Santa Barbara, California 93106, USA.
Langmuir. 2006 Sep 12;22(19):8156-62. doi: 10.1021/la0607499.
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 ( approximately 100%) and more stable than liposomes without encapsulated cisplatin. Cisplatin-encapsulated liposomes of approximately 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.
顺铂是针对多种癌症最有效的细胞毒性药物。然而，由于其在靶细胞中的摄取效率低下，其应用受到限制。据报道，顺铂的脂质体制剂可部分克服这一限制。脂质体 - 顺铂制剂的物理化学特性，包括其大小、稳定性、包封效率和细胞质内化效率，在脂质体制剂的有效应用中起着重要作用。我们使用原子力显微镜（AFM）来确定顺铂包封脂质体的物理化学特性，使用AFM和荧光显微镜来检查它们的细胞质内化，并使用活/死检测来检查它们的细胞毒性。未包封的顺铂呈球形，大小为10 - 50纳米。AFM力剖析和硬度测量表明，顺铂包封的脂质体比未包封顺铂的脂质体明显更硬（约100%）且更稳定。直径约250纳米的顺铂包封脂质体（纳米脂质体）最有效地被内化，并以时间依赖性方式诱导细胞毒性。尺寸相似但没有顺铂的脂质体，尽管被内化到细胞质中，但不会诱导细胞毒性。
