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.

In vitro and in vivo study of a nanoliposomal cisplatin as a radiosensitizer

“…12 Ramachandran et al also found that the uptake of nanoparticle formations of CDDP by cells was much easier. 13 CDDP is a radiation sensitizer and has been widely used with radiation therapy for cancer treatment.…”

Microfluidic hydrodynamic focusing based synthesis of POPC liposomes for model biological systems

“…For example, the interaction of particles with some cell types is known to vary with particle size [47,48]. Thus, fine control over liposome size can be exploited to produce optimal drug and gene delivery vectors [2,5]. Liposome geometry is also expected to play a significant role in their application as model biological systems.…”

“…Since their discovery in the 1960s [1], liposome application has spanned a wide range of fields. They have been used as gene and drug delivery vectors in the pharmaceutical industry [2][3][4][5], as contrast agent containers in enhanced medical imaging [6][7][8], and as nano-sized crystallization reactors [9,10]. Similarities in the chemical and physical properties of the lipid bilayers of liposomes and living cells have also led to their use as models in studying cellular membranes [1,11].…”

Electrohydrodynamic fabrication of core–shell PLGA nanoparticles with controlled release of cisplatin for enhanced cancer treatment

“…4 Therefore, the development of a controlled release drug delivery system for CDDP represents a key challenge in achieving optimum clinical response for this potent chemotherapy agent. 5 In recent years, the continued search for effective cancer treatment has led to the emergence of many nanosized vectors for the delivery of chemotherapeutics, for example, liposomes 6 and polymeric particles, 7,8 which aim to reduce premature interaction with the biological environment and improve cellular targeting. 9,10 Importantly, the physicochemical properties of nanovectors influence their efficacy as drug delivery systems.…”