Short-Chain Glycoceramides Promote Intracellular Mitoxantrone Delivery from Novel Nanoliposomes into Breast Cancer Cells

Abstract

Nanoliposomal encapsulation improves intratumoral MTO delivery over free drug. Liposome bilayer-incorporated SCS preferentially permeabilize tumor cell membranes enhancing intracellular MTO delivery.

Plasma membrane targeting by short chain sphingolipids inserted in liposomes improves anti-tumor activity of mitoxantrone in an orthotopic breast carcinoma xenograft model

“…SCS upon their insertion into cell membranes exerts drug transport enhancing properties to amphiphilic drugs such as Doxorubicin (Dox) and MTO [14,[19][20][21][22]33]. SCS preferentially exerts these properties toward tumor cell membranes, a phenomenon which is likely related to an aberrant makeup of these membranes in comparison with those of normal cells [14,21,22]. A tumor cell selectivity has been observed for the drug uptake enhancing effect of SCS [21,34].…”

“…Lipid film was hydrated by addition of 250 mM of (NH 4 ) 2 SO 4 , pH 5.5 and liposomes were sized by sequential extrusion through 100-, 80-, and 50 nm polycarbonate filters (Northern Lipids, Vancouver, Canada). Non-encapsulated (NH 4 ) 2 SO 4 was removed by gel filtration chromatography using PD-10 Sephadex column, eluted with 135 mM NaCl, 10 mM Hepes buffer, pH 7.4 and drug loading was performed for 1 h at 65°C, at a drug to phospholipid ratio (D:PL) of 0.07 (w/w) [14]. Size and polydispersity index (PDI) were determined by dynamic light scattering using a Zetasizer Nano ZS (Malvern Instruments, Worcestershire, UK) at 25°C.…”

“…To overcome these barriers, we questioned whether the membrane barrier function could be modulated to specifically enhance drug membrane traversal and increase its intracellular accumulation and thus its therapeutic efficacy. Here we aim to apply our previously described concept of targeting the plasma membrane lipid composition using short chain sphingolipids (SCS) [14] as novel drug delivery strategy to improve MTO chemotherapy for breast cancer. To achieve this we made use of a nanovesicle platform with pegylated-bilayer-inserted SCS and MTO encapsulated in its aqueous core [14].…”

“…Here we aim to apply our previously described concept of targeting the plasma membrane lipid composition using short chain sphingolipids (SCS) [14] as novel drug delivery strategy to improve MTO chemotherapy for breast cancer. To achieve this we made use of a nanovesicle platform with pegylated-bilayer-inserted SCS and MTO encapsulated in its aqueous core [14]. Liposomes composed of DSPE-PEG2000 have good solubility properties in aqueous media preventing liposomal clearance by Mononuclear Phagocytic System (MPS) in spleen and liver by inhibition of nanocarrier recognition.…”

Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

“…[1][2][3][4] MIT has a structure similar to that of anthracyclines, which induces the mitochondrial apoptosis pathway and hinders proliferation by causing DNA damage and disrupting DNA repair or synthesis. 2,5 In order to enhance the anticancer activity with a low dosage of MIT, we used nanoscale drug carriers to deliver MIT to the cancer cells in this study.…”