Oestrogen receptor-mediated liposomal drug delivery for treating melanoma

Area of Science:

• Oncology
• Nanotechnology
• Pharmacology

Background:

• Oestrogen receptor (ER) is a therapeutic target in various cancers beyond gynaecological malignancies.
• Previous development of oestrogen-targeting molecule ES-C10 showed efficacy in ER-positive breast and skin cancers.

Purpose of the Study:

• To explore the targeting potential of ES-C10 as a ligand in liposomal formulations.
• To evaluate the additive cytotoxic effects of ES-C10-incorporated liposomes (DCME and DCDE) carrying anticancer agents MCIS3 and Docetaxel™.
• To assess the ER-mediated cytotoxicity and apoptosis induction in ER-positive cancer cells.

Main Methods:

• Incorporation of ES-C10 ligand into two distinct liposomal formulations (DCME and DCDE) carrying specific anticancer drugs.
• Assessment of cytotoxicity in ER-positive, ER-negative, and non-cancer cell lines.
• Evaluation of ER-mediated effects, apoptosis induction (caspase 3), and key protein level changes (pAkt, PTEN, p53).
• Analysis of haemolytic activity and biodistribution of liposomes in vivo.

Main Results:

• DCME and DCDE liposomes demonstrated enhanced cytotoxicity against ER-positive cancer cells compared to ER-negative or non-cancer cells.
• Liposomes induced ER-mediated cytotoxicity and caspase 3-dependent apoptosis in ER-positive melanoma cells.
• Treatment led to decreased pAkt and increased PTEN and p53 levels.
• Targeted liposomes showed minimal haemolysis, selective tumor drug delivery, improved anti-tumor effects, and increased survival rates.

Conclusions:

• Development of two novel liposomal drug delivery systems utilizing an oestrogen-based ligand (ES-C10).
• These systems achieve efficient, ER-mediated anti-melanoma effects through targeted delivery.
• The findings support the potential of ER-targeted liposomes for treating ER-expressing cancers.