Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity.
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.
Ramachandran
Srinivasan
S
Neuroscience Research Institute, University of California at Santa Barbara, Santa Barbara, California 93106, USA.
Quist
Arjan P
AP
Kumar
Sashi
S
Lal
Ratnesh
R
D002214:Capsules / Q000737:chemistry*; D016923:Cell Death; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002945:Cisplatin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D004705:Endocytosis; D005260:Female; D005453:Fluorescence; D006801:Humans; D008081:Liposomes; D018625:Microscopy, Atomic Force; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy
D002214:Capsules; D008081:Liposomes; D002945:Cisplatin