Nanoparticle-Functionalized Acrylic Bone Cement for Local Therapeutic Delivery to Spinal Metastases

Abstract

AbstractPolymethylmethacrylate bone cement is often used to reconstruct critical-sized defects generated by surgical resection of spinal metastases. Residual tumor cells after a resection can drive recurrence and destabilization. Doxorubicin (DOX) is a common chemotherapeutic drug with unwanted side-effects when administered systemically. Mesoporous silica nanoparticles are gaining attention for targeted drug delivery to bypass the negative side effects associated with systemic drug administration. We developed a nanoparticle-functionalized cement for the local release of DOX and tested its ability to suppress cancer cells. DOX was loaded onto nanoparticles which were then mixed into the cement. Drug release profiles were obtained over a period of 4 weeks. Cement constructs were incubated with 2D and 3D cultures of breast and prostate cancer cell lines, and cell metabolic activity and viability were evaluated. Cell migration and spheroid growth were assessed in collagen-coated spheroid cultures. Nanoparticles were homogenously dispersed and did not alter cement mechanical strength. A sustained DOX release profile was achieved with the addition of nanoparticles to the bone cement. The release profile of DOX from nanoparticle cement may be modified by varying the amount of the drug loaded onto the nanoparticles and the proportion of nanoparticles in the cement. Cells treated with the cement constructs showed a dose- and time-dependent inhibition. Cell migration and spheroid growth were impaired in 3D culture. We show that nanoparticles are essential for sustained DOX release from bone cement. DOX-loaded nanoparticle cement can inhibit cancer cells and impair their migration, with strong potential forin vivotranslation studies.