Background: Drugs based on synthetic lethality have advantages such as inhibiting
tumor growth and affecting normal tissue in vivo. However, specific targets for
osteosarcoma have not been acknowledged yet. In this study, a non-targeted but controllable drug delivery system has been applied to selectively enhance synthetic lethality in
osteosarcoma in vitro, using the magnetic-driven
hydrogel microrobots. Methods: In this study,
EPZ015666, a PRMT5 inhibitor, was selected as the synthetic lethality drug. Then, the drug was carried by
hydrogel microrobots containing Fe3O4. Morphological characteristics of the microrobots were detected using electron microscopy. In vitro drug effect was detected by the
CCK-8 assay kit, Western blotting, etc. Swimming of microrobots was observed by a timing microscope. Selective inhibition was verified by cultured
tumors in an increasing magnetic field. Results: Genomic mutation of MTAP deletion occurred commonly in pan-
cancer in the TCGA database (nearly 10.00%) and in
osteosarcoma in the TARGET database (23.86%). HOS and its derivatives, 143B and HOS/
MNNG, were detected by MTAP deletion according to the CCLE database and RT-PCR.
EPZ015666, the PRMT5 inhibitor, could reduce the SDMA modification and inhibition of
tumor growth of 143B and HOS/
MNNG. The
hydrogel microrobot drug delivery system was synthesized, and the drug was stained by
rhodamine. The microrobots were powered actively by a magnetic field. A simulation of the selected inhibition of microrobots was performed and lower cell viability of
tumor cells was detected by adding a high dose of microrobots. Conclusion: Our magnetic-driven drug delivery system could carry synthetic lethality drugs. Meanwhile, the selective inhibition of this system could be easily controlled by programming the strength of the magnetic field.