Coassembled Nanoparticles Composed of Functionalized Mesoporous Silica and Pillar[5]arene-Appended Gold Nanoparticles as Mitochondrial-Selective Dual-Drug Carriers

Coassembled nanoparticles composed of functionalized mesoporous silica and pillar5]arene-appended Au nanoparticles obtained through the formation of a host–guest complex are designed and synthesized as a mitochondrial-selective dual-drug delivery system. A pyridinium-based ligand and fluorescein isothiocyanate are immobilized onto mesoporous silica to act as the mitochondria-targeting ligand and fluorescence tracker, respectively, of a material dubbed NP-3. Carboxylated pillar5]arene-capped Au nanoparticles (CP-AuNPs) are fabricated by the templated reduction of Au³⁺. Interestingly, coassembled nanoparticles (NP-1) composed of doxorubicin (DOX) loaded NP-3 and CP-AuNPs are then prepared via the formation of a host–guest complex between the pyridinium-based ligand of NP-3 and the pillar5]arene of CP-AuNPs. To demonstrate the effectiveness of NP-2 and NP-1 as mitochondrial targeting drug delivery systems, DOX and F16 are employed as model drugs. These drugs loaded onto NP-2 and CP-AuNPs, respectively, are selectively delivered to mitochondria, indicating the usefulness of NP-2 and CP-AuNPs as mitochondrial-specific drug-delivery carriers in cancer cells. More interestingly, the use of NP-1 is also associated with the selective accumulation of DOX and F16 in mitochondria. The selective mitochondrial-targeting of NP-1 is possible by NP-2 and F16 exposed to the cytoplasm, allowing the codelivery of the two drugs to the mitochondria.