Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate

Abstract

Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.

Synthesis, Characterization and Antioxidant Properties of a New Lipophilic Derivative of Edaravone

“…These data suggest that C18-EdV may work as a good antioxidant in cellular systems as well as in cell-free systems, resulting in promise for use as a novel therapeutic drug candidate in the treatment of diseases associate with oxidative stress. Further studies are in progress in our research group looking for a possible prediction of the structure and stability of the C18-EdV liposomes by means of computational protocols already assessed [41,42,43,44,45,46,47], in order to design, at a molecular level, efficient antioxidant nanovectors.…”

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

“…The stabilization of EGCG can be obtained by different approaches including the employment of reducing agents, structural modification and/or drug delivery systems [12][13][14]. Among these, the application of derivatization strategies designed to increase the molecule hydrophobicity and the interaction with cellular membrane [15][16][17][18][19][20] is considered as a feasible approach to improve the activity of bioactive molecules.…”

Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-Gallate: An In-Silico/Experimental Approach

“…Nanostructures made of amphiphilic natural or synthetic lipids are biocompatible and biodegradable platforms for drug delivery [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Among them, liposomes have emerged as highly promising self-assembled nanovectors able to entrap both lipophilic and hydrophilic agents in the lipid membrane and in the aqueous core, respectively [ 10 ].…”