UV radiation enhanced encapsulation of superparamagnetic iron oxide nanoparticles (MNPs) in microparticles derived from tumor repopulating cells

Extracellular vesicles (EVs) such as microparticles secreted by the cells can be manipulated and used for delivering therapeutic drugs to target and eradicate cancer cells. However, high encapsulation efficiency and mass production of the microparticles remain difficult to achieve. Efficient and targeted delivery to cancer cells is another hurdle to be addressed. To overcome these issues, we integrated superparamagnetic iron oxide nanoparticles (MNPs) with microparticles. First of all, exposure of highly aggressive tumor-repopulating cells (TRC) to UV radiation dramatically improved microparticle production. These TRC cells were selected from diverse cancer cell lines that are 3D culturing in soft fibrin gel. These microparticles derived from 3D-cultured TRCs have lower membrane stiffness than 2D-cultured cells. Ferrozine assay showed that endocytosis and encapsulation of MNPs during microparticle production were higher in 3D-cultured TRC cells than in 2D cultured cells. Packaging of MNPs into microparticles also enhanced cellular uptake of MNPs without inducing cytotoxicity to treated cells. Compared to the naked MNPs, ex vivo fluorescence imaging shows that mice tail-vein injected with microparticle-encapsulated MNPs displayed continuous increments of intratumoral accumulation of MNPs. Furthermore, MRI images revealed a higher T2 contrast and an uneven distribution of the T2 contrast in the tumor of mice tail-vein injected with microparticle-encapsulated MNPs than naked MNPs. This study provides a new platform for cancer imaging by integrating MNPs and microparticles derived from tumor-repopulating cells.