Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

Abstract

Triple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells’ proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.

Diagnostic value of ultrasound elastography in triple negative breast cancer: A meta-analysis

“…Due to its benign early imaging features and rapid growth, it is found in the middle and late stages, and there is no targeted treatment due to the lack of effective targets, which has always been a difficult problem in clinical practice. [ 23 ] In recent years, with the improvement of the resolution of ultrasound instruments and the diversification of imaging modes, the exploration of breast imaging has been continuously improved.…”

Chemical conjugation of aptamer–sphingomyelin nanosystems and their potential as inhibitors of tumour cell proliferation in breast cancer cells

“…In brief, preparation was carried out in two steps: firstly, covalent conjugation/binding between PEG and aptamer sequence was performed (attending to the reactive groups of each other and specifications described below) in a ratio of 5 : 1 (PEG : aptamer). Next, the nanoemulsion was formed following the ethanol injection method slightly modified 26,51,52 by adding the organic phase (containing stock solutions of vitamin E and Sphingomyelin at 200 and 40 mg mL −1 in ethanol, respectively) to the aqueous phase composed of the PEG-aptamer conjugate, resulting in a molar ratio of VitE : SM : PEG of 1 : 0.1 : 0.01. All nanoconjugate formulations were scaled up to a final volume of 400 µL.…”

Lipid-Based Nanoparticles as a Pivotal Delivery Approach in Triple Negative Breast Cancer (TNBC) Therapy

“…Furthermore, it was observed that the ET-NEs penetrated the physiological barriers of MDA-MB 231 xenografted zebrafish embryos, resulting in a significant reduction of cancer cell proliferation, which was further confirmed by confocal laser microscopy. Further, it was observed that the ET-NEs showed a dose-dependent IC 50 which was found to be 6.9 μg/mL at 13.2 μM after 24 h of incubation, whereas the free ET showed a higher IC 50 which is 13.9 μg/mL at 26.5 μM [ 65 ].…”