Magnetic　nanoparticles　are　promising　materials　for　a　variety　of　applications,　especially　in　the　delivery　and　controlled　release　of　various　drugs.　These　compounds　present　a　major　obstacle　to　the　treatment　of　many　diseases　and　have　a　pivotal　role　in　the　future　of　personalized　medicine.　In　the　present　study,　adsorption　and　delivery　of　acyclovir　(ACV)　on　pristine　and　modified　magnetic　nanoparticles　are　investigated.　The　as-synthesized　magnetite　nanoparticles　are　decorated　with　3-(triethoxysilyl)-propylamine　prior　loading　of　ACV　and　samples　are　characterized　by　means　of　SEM,　TEM,　VSM,　DLS,　and　zetametry　studies.　VSM　and　zeta　potential　studies　show　that　ACV　decreases　the　saturation　magnetization　and　zeta　potential　of　magnetite　nanoparticles.　Then,　adsorption　of　ACV　in　phosphate　buffered　saline　was　examined　and　effects　of　some　variables　including　pH,　loading　time　and　temperature　are　briefly　investigated.　Our　experimental　results　revealed　the　best　loading　(~80%)　can　be　achieved　at　pH　9　at　39　°C　after　5　h.　The　loading　efficacy　may　be　assigned　to　the　increment　of　hydrogenic　interactions　under　the　loading　process.　Eventually,　a　DFT　study　was　fully　investigated　to　provide　important　theoretical　parameters　related　to　the　adsorption　process.　The　performed　computations　on　pristine　and　doped　Fe3O4　nanoparticles　prove　strong　interactions　between　nitrogen　and　oxygen　atoms　of　acyclovir　with　Fe+3　ions　of　magnetic　nanoparticles.　Moreover,　additional　hydrogen　bonds　between　active　sites　of　the　adsorbed　drug　molecule　and　Fe3O4　fragments　lead　to　a　significant　adsorption　and　stabilization　of　the　obtained　configurations.　The　nature　of　intermolecular　interactions,　electron　densities,　and　Laplacians　is　also　fully　investigated　at　the　bond　critical　points.　Natural　bond　orbital　analysis　confirms　that　acyclovir　can　be　adsorbed　on　the　surface　of　Fe3O4　nanoparticle　with　a　charge　transfer　from　acyclovir　to　the　nanoparticle.　In　addition,　the　modified　and　doped　Fe3O4　nanoparticles　can　absorb　drug　molecules　more　strongly　compared　to　the　pristine　counterpart　and　generate　stable　configurations.　Interestingly,　doping　with　Zn　atom　results　in　an　electronic　hole,　hence,　the　conductivity　of　the　Fe3O4　may　be　enhanced.　Therefore,　Zn　impurities　can　introduce　local　states　inside　the　Eg　and　improve　reactivity　of　magnetic　nanostructures　towards　adsorption　process.　Therefore,　the　examined　metal-doped　magnetic　nanoparticles　in　this　study　can　be　applied　as　promising　nanobiosensors　for　detection　and　delivery　of　ACV　in　medicine.　©　2020　The　Authors