Human and canine osteosarcoma cell lines: How do they react upon incubation with calcium phosphate-coated lipid nanoparticles carrying doxorubicin and curcumin?

Abstract

Osteosarcoma (OSA) is a bone cancer that affects both humans and animals, with dogs being particularly vulnerable. Standard therapy is often limited by multidrug resistance (MDR), primarily due to the overexpression of P-glycoprotein (P-gp), which expels drugs from the cells, reducing their efficacy. To overcome this challenge, drug delivery systems (DDS) and P-gp modulators have been explored. However, developing DDS that selectively target cancer cells remains difficult, with many current options lacking efficiency. Our research group has recently developed an innovative type of nanoparticle with a lipid core and a calcium phosphate shell (CaP-NPs), which enhances the uptake of doxorubicin (DOXO) in OSA cells. In this study, we loaded a lipophilic ester of doxorubicin (C12DOXO) and curcumin (CURC), a natural P-gp modulator, into CaP-NPs and co-incubated them into human and canine OSA cell lines, including DOXO-resistant cells. The results demonstrated a significant reduction in viability in human OSA cells. Additionally, the combination treatment led to a further increase in C12DOXO retention when cells were also treated with the P-gp inhibitor verapamil, indicating enhanced efficacy against MDR mechanisms. Notably, canine OSA cells exhibited a distinct response pattern, suggesting the presence of species-specific differences that warrant further investigation.