Polymeric micelles for the encapsulation and delivery ofanti-cancer stem cell metal complexes

Cancer stem cells (CSCs) are tumour-initiating cells that can be responsible for metastasis and relapse. In our group, metal complexes with promising anti-CSCs properties have been successfully synthesised and characterised. However, their poor solubility in aqueous solutions can affect their internalisation by cells and their therapeutic potential. A well-established strategy to improve the solubility of lipophilic compounds is encapsulation into biodegradable micelles. Elongated-shape micelles (filomicelles) are less prone to be recognised by immune cells, leading to a longer circulating time in the blood and increased accumulation in the tumour. In vivo studies have shown that filomicelles are able to effectively deliver anti-tumoral agents to tumours in mice. This project aims to prepare and characterise spherical poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) micelles and poly(ethylene glycol)–poly(caprolactone) (PEG-PCL) filomicelles containing anti-CSCs metal complex complexes. The anti-CSC activity of the nanoparticle formulations and their ability to deliver their cargo into CSCs will be studied.

An immunogenic copper(II) complex has been successfully encapsulated into PLGA-PEG nanoparticles by nanoprecipitation and characterised by imaging and analytical methods. The polymeric envelope increased CSCs uptake and potency relative to the free copper(II) complex.

The same copper(II) complex was encapsulated in PEG-PCL filomicelles using various self-assembly techniques. The morphology of the different formulations were characterised by transmission electron microscopy (TEM). The formulation obtained by solvent evaporation method was employed for biophysical and biological studies and its potency towards CSCs was compared to the spherical formulation.

Finally, an anti-osteosarcoma stem cells (OSCs) gallium(III) agent was encapsulated into PEG-PLGA spherical nanoparticles by nanoprecipitation and characterised by imaging and analytical methods. The polymeric envelope increased potency relative to the free gallium(III) complex and maintained its mechanism of action.