Mithramycin delivery systems to develop effective therapies in sarcomas.

Area of Science:

• Drug delivery systems
• Nanomedicine
• Oncology

Background:

• Sarcomas are aggressive cancers with limited treatment options.
• Mithramycin (MTM) shows anti-tumor activity but has poor toxicity.
• Drug repositioning is a strategy to find new cancer therapies.

Purpose of the Study:

• To develop novel nanocarrier formulations for improved MTM delivery.
• To enhance the therapeutic index of MTM for sarcoma treatment.
• To evaluate the efficacy and safety of MTM-loaded nanocarriers.

Main Methods:

• MTM was loaded into polylactide (PLA) nanoparticles (NPs), liposomes (LIP), and hydrogels (HG).
• Nanoparticle characterization included hydrodynamic radius and polydispersity index.
• In vitro cytotoxicity, anti-invasive, and anti-stemness assays were performed.
• In vivo efficacy was assessed in mice bearing sarcoma xenografts.

Main Results:

• MTM-loaded NPs and LIP showed optimal size and high encapsulation efficiencies.
• Formulations exhibited varying release rates: fast for HG, sustained for NPs and LIP.
• All MTM formulations retained anti-cancer properties in vitro.
• Encapsulated MTM demonstrated enhanced therapeutic effects and better tolerability in vivo.

Conclusions:

• Novel nanocarrier formulations offer an efficient and safer alternative for MTM delivery in sarcoma treatment.
• These formulations have the potential to improve patient outcomes for sarcoma.