title: Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity.
abstract: 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.
authors.affiliation: Neuroscience Research Institute, University of California at Santa Barbara, Santa Barbara, California 93106, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Arjan P
authors.initials: AP
authors.lastname: Quist
authors.forename: Sashi
authors.initials: S
authors.lastname: Kumar
authors.forename: Ratnesh
authors.initials: R
authors.lastname: Lal
mesh_terms: 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
chemical_list: D002214:Capsules; D008081:Liposomes; D002945:Cisplatin