A Triple Co-Delivery Liposomal Carrier That Enhances Apoptosis via an Intrinsic Pathway in Melanoma Cells.

Nina Filipczak,Adriana Piwoni,Mohamed Mahmud,Vladimir Torchilin,Anna Jaromin,Can Sarisozen,Jerzy Gubernator

doi:10.3390/cancers11121982

Nina Filipczak, Adriana Piwoni + Show 5 more

Open Access

https://doi.org/10.3390/cancers11121982

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Abstract

The effectiveness of existing anti-cancer therapies is based mainly on the stimulation of apoptosis of cancer cells. Most of the existing therapies are somewhat toxic to normal cells. Therefore, the quest for nontoxic, cancer-specific therapies remains. We have demonstrated the ability of liposomes containing anacardic acid, mitoxantrone and ammonium ascorbate to induce the mitochondrial pathway of apoptosis via reactive oxygen species (ROS) production by the killing of cancer cells in monolayer culture and shown its specificity towards melanoma cells. Liposomes were prepared by a lipid hydration, freeze-and-thaw (FAT) procedure and extrusion through polycarbonate filters, a remote loading method was used for dug encapsulation. Following characterization, hemolytic activity, cytotoxicity and apoptosis inducing effects of loaded nanoparticles were investigated. To identify the anticancer activity mechanism of these liposomes, ROS level and caspase 9 activity were measured by fluorescence and by chemiluminescence respectively. We have demonstrated that the developed liposomal formulations produced a high ROS level, enhanced apoptosis and cell death in melanoma cells, but not in normal cells. The proposed mechanism of the cytotoxic action of these liposomes involved specific generation of free radicals by the iron ions mechanism.

Highlights

Melanoma, one of the most aggressive types of cancer, arises from the transformation of normal melanocytes
Tested liposomal formulations containing 5 mol% of the AA with MTX encapsulated by means of an ammonium ascorbate gradient exhibited remarkably high toxicity toward both used melanoma cancer lines, but not to non-cancer NHDF cells, where the protective influence of ascorbate was observed.The main purpose of this research was to develop liposomes co-loaded with anacardic acid, mitoxantrone and ammonium ascorbate, and investigate the combined effects of these liposomal formulations on human melanoma cancer cells
Morphological analysis determined by TEM microscopy confirmed the presence of circular structures with uniform size in AA-containing liposome samples (Figure 1)

Summary

Introduction

One of the most aggressive types of cancer, arises from the transformation of normal melanocytes. This type of cancer is characterized by uncontrolled divisions, dysregulation of cell processes and the ability to invade and create metastases even at an early stage of development [1,2]. The basic method of treating melanoma is the surgical removal of the neoplastic lesions with a margin of healthy tissue. Despite aggressive treatment, complete remission is often not observed. The prognosis depends on the depth of tumor cell infiltration and the clinical stage of the cancer.

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