Rational design of nanosystems for simultaneous drug delivery and photodynamic therapy by quantum mechanical modeling

Drug delivery systems are based on reversible interactions between carriers and drugs. Spacers are oftenintroduced to tailor the type of interaction and to keep drugs intact. Here, we model a drug deliverysystem based on a functionalized curved TiO2nanoparticle of realistic size (700 atoms–2.2 nm) by theneurotransmitter dopamine to carry the anticancer chemotherapeutic agent doxorubicin (DOX). The mul-tiscale quantum chemical study aims at unraveling the nature and mechanism of the interactions betweenthe components and the electronic properties of the composite system. We simulate the temperatureeffect through molecular dynamics runs of thermal annealing. Dopamine binds preferentially to low co-ordinated Ti sites on the nanoparticle through dissociated bidentate and chelate modes involving the diolgroups. DOX is tethered by H-bonds,π–πstacking, dipole–dipole interactions and dispersion forces.Comparing different coverage densities of the spacer on the nanoparticle surface, we assess the bestconditions for an effective drug transport and release: only at full coverage, DOX does not slip among thedopamine molecules to reach the nanoparticle surface, which is crucial to avoid the formation of stablecoordinative bonds with under-coordinated Ti atoms. Finally, given the strong absorption properties andfluorescence of DOX and of the TiO2photocatalyst, we model the effect of light irradiation throughexcited state calculations to localize excitons and to follow the charge carrier’s life path. This fundamentalstudy on the nature and mechanism of drug/carrier interaction provides a solid ground for the rationaldesign of new experimental protocols for a more efficient drug transport and release and its combinationwith photodynamic therapy.