Magnetic-Driven Hydrogel Microrobots Selectively Enhance Synthetic Lethality in MTAP-Deleted Osteosarcoma

Abstract

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.

Application of micro/nanorobot in medicine

“…These microrobots are often embedded with magnetic particles or affixed with permanent magnets, allowing for precision control by modulation of magnetic field direction and intensity to realize targeted therapeutic delivery. Mu et al (2022) devised a hydrogel-based microrobot for drug delivery, utilizing a synthetic lethal drug that, while inherently cytotoxic to normal cells, is guided by genomic markers. Through magnetic manipulation, the microrobot devised by Mu and others can be steered with precision to tumor sites, thereby mitigating adverse effects and augmenting the efficacy of drug delivery.…”

Stimuli-responsive microcarriers and their application in tissue repair: A review of magnetic and electroactive microcarrier

“…And Ciofani et al [ 50 ] used magnetic Alg microspheres carrying NGF to induce PC12 differentiation which opened new therapeutic options for neuronal regeneration. Magnetic microcarriers are also used in anti-tumor [ 51 , 52 ] and wound healing [ [53] , [54] , [55] ] which can specifically recognize growth factors and encapsulate drugs. However, this review focuses on tissue repair, so cancer treatment will not be elaborated.…”

Magnetic propelled hydrogel microrobots for actively enhancing the efficiency of lycorine hydrochloride to suppress colorectal cancer

“…The magnetic-driven microrobots that achieves precise manipulation by changing the strength and direction of the magnetic field has great potential for clinical application in drug treatment of tumors, which has aroused great interest among researchers ( Li et al, 2017 ; Wang et al, 2020 ; Ji et al, 2021 ; Zhang et al, 2023 ; Li et al, 2023 ). By precisely controlling the magnetic field, microrobots can be guided to the tumor site and release drugs, which not only greatly improves the therapeutic effect of drugs, but also significantly reduces a series of problems such as drug cytotoxicity and serious complications ( Chen et al, 2018 ; Mu et al, 2022 ; Wang et al, 2022 ). This technology is expected to provide new solutions for tumor treatment in the future ( Wang et al, 2021 ).…”