Decoration of Squalenoyl-Gemcitabine Nanoparticles with Squalenyl-Hydroxybisphosphonate for the Treatment of Bone Tumors

Therapeutic perspectives of bone tumors such as osteosarcoma remain restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancer squalene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was synthetized by chemical conjugation of a 1-hydroxyl-1,1-bisphosphonate moiety to the squalene chain. This amphiphilic compound was inserted onto squalenoyl-gemcitabine nanoparticles using the nanoprecipitation method. The co-assembly led to nanoconstructs of 75 nm, with different morphology and colloidal properties. The presence of squalenyl-hydroxybisphosphonate enhanced the nanoparticles binding affinity for hydroxyapatite, a mineral present in the bone. Moreover, the in vitro anticancer activity was preserved when tested in commercial and patient-treated derived pediatric osteosarcoma cells. Further in vivo studies will shed light on the potential of these nanomedicines for the treatment of bone sarcomas.

Automated summary

A novel bone-affine squalene-based nanomedicine was developed by conjugating a hydroxybisphosphonate moiety to the squalene chain and inserting it into squalenoyl-gemcitabine nanoparticles. The presence of squalenyl-hydroxybisphosphonate enhanced nanoparticles' binding affinity for hydroxyapatite in bones and preserved their anticancer activity in vitro. Further in vivo studies are needed to explore the potential of these nanomedicines for treating bone sarcomas.