Targeting of lysosomes by liposomes modified with octadecyl-rhodamine B

Abstract

The use of lysosome-targeted liposomes may significantly improve a delivery of therapeutic enzymes into lysosomes for the treatment of lysosome-associated diseases. The aim of this research was to achieve a specific intracellular targeting of lysosomes, by using liposomes modified with the lysosomotropic octadecyl-rhodamine B (RhB) and loaded with a model compound, fluorescein isothiocyanate (FITC)–dextran (FD). Plain and RhB-modified liposomes were prepared by hydration of lipid films and loaded with FD or with 5-dodecanoylaminofluorescein di-β-D-galactopyranoside (C12FDG), a specific substrate for the intralysosomal β-galactosidase. The delivery of these liposomes and their content to lysosomes in HeLa cells was investigated by confocal microscopy, flow cytometry, and subcellular fractionation. Confocal microscopy demonstrated that RhB-liposomes co-localize well with the specific lysosomal markers, unlike plain liposomes. The comparison of the FITC fluorescence of the lysosomes isolated by subcellular fractionation also showed that the efficiency of FD delivery into lysosomes by RhB-modified liposomes was significantly higher compared with plain liposomes. These results were additionally confirmed by the flow cytometry of the intact cells treated with C12FDG-loaded liposomes that also demonstrated increased lysosomal targeting by RhB-modified liposomes. The modification of the liposomal surface with a lysosomotropic ligand, such as octadecyl-RhB, can significantly increase the delivery of liposomal loads to lysosomes.

Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery

“…Cell lysosomes have been targeted with NDDSs modified with octadecyl-rhodamine B 121 . Cytotoxic ceramides have been delivered to lysosomes of cancer cells using transferrin-modified liposomes, which resulted in reduced tumour growth in mice bearing an ovarian carcinoma xenograft 66 .…”

Current Trends in The Use of Liposomes for Tumor Targeting

“…prepared fluorescein isothiocyanate-dextran-loaded lysosome-targeted liposomes surface modified with a lysosomotropic ligand, octadecyl rhodamine B. The modified liposomes successfully delivered the loaded cargo to lysosomes as observed through their colocalization with a lysosomal marker and a twofold higher fluorescence of the lysosome-enriched fractions treated with modified liposomes compared with unmodified ones was observed in HeLa cells [101]. Ceramides are useful tools in inducing lysosomal membrane permeabilization; futhermore, intracellular delivery of ceramides via Tf-conjugated liposomes enhanced apoptosis in vitro in HeLa cells and in vivo in an A2780 ovarian carcinoma xenograft mouse model [49].…”

Lysosomes and Nanotherapeutics: Diseases, Treatments, and Side Effects

“…octadecyl-rhodamine B (Rh)) and loaded with velaglucerase alfa (VPRIV™) for ERT of Gaucher disease type I were shown to improve uptake by monocytes and fibroblasts in culture, accumulation in lysosomes, and enzymatic activity. [168][169][170] Apart from liposomes, limited work has been published on the use of other drug delivery systems for LSD enzyme replacement. At the micro-scale, calcium alginate microspheres loaded with glucocerebrosidase have been Table 3.…”