Cubosomal lipid formulation for combination cancer treatment: delivery of chemotherapeutic agent and complexed α-particle emitter 213Bi

Here, we propose tailored lipid liquid-crystalline carriers (cubosomes), which incorporate an anticancer drug (doxorubicin) and complexed short-lived α-emitter (bismuth-213), as a strategy to obtain more effective action toward the cancer cells. Cubosomes were formulated with doxorubicin (DOX) and an amphiphilic ligand (DOTAGA-OA), which forms stable complexes with 213Bi radionuclide. The behavior of DOX incorporated into the carrier together with the chelating agent was investigated, and the drug liberation profile was determined. The experiments revealed that the presence of the DOTAGA-OA ligand affects the activity of DOX when they are incorporated into the same carrier. This unexpected influence was explained based on the results of release studies, which proved the contribution of electrostatics in molecular interactions between the positively charged DOX and negatively chargedDOTAGA-OA in acidic and neutral solutions. A significant decrease in the viability of HeLa cancer cells was achieved using sequential cell exposure: first to the radiolabeled cubosomes containing 213Bi complex and next to DOX-doped cubosomes.Therefore, the sequential procedure for the delivery of both drugs encapsulated in cubosomes is suggested for further biological and in vivo studies

CYTRYNIAK Adrianna;  ŻELECHOWSKA-MATYSIAK Kinga;  NAZARUK Ewa;  BILEWICZ Renata;  WALCZAK Rafal;  MAJKA Emilia;  MAMES Adam;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  BILEWICZ Aleksander;  MAJKOWSKA-PILIP Agnieszka; 

2022-12-19

AMER CHEMICAL SOC

JRC129873

1543-8384 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC129873,   

10.1021/acs.molpharmaceut.2c00182 (online),