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

Abstract

Coassembled nanoparticles composed of functionalized mesoporous silica and pillar[5]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 pillar[5]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 pillar[5]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.

Supramolecular Biopharmaceutical Carriers Based on Host–Guest Interactions

“…Ahn and co-workers designed mesoporous silica modified by a pyridinium-based ligand and fluorescein isothiocyanate and carboxylated pillar [5]arenecapped Au nanoparticles (CP-AuNPs) prepared by template reduction method both to form host−guest complex nanodrug carriers (Figure 12). 77 Subsequently DOX encapsulated into silica and F16 encapsulated into the pillar [5]arene via host− guest interaction were coassembled into nanoparticles (NP-1), respectively. CLSM images of HeLa cells treated with the dual drug carrier NP-1 (carrying DOX and F16) and absorbance changes over time in the presence of GSH at pH 7 show that NP-1 behaves as a DOX-to-mitochondria nanocarrier, while F16 selectively accumulates in the mitochondria.…”

Multifunctional Pillar[n]arene-Based Smart Nanomaterials

“…PA–smart drug delivery systems (DDS) have been developed through the functionalization of porous materials and nanoparticles. For instance, mesoporous silica nanoparticles (MSNs) have been grafted with PAs via the electrostatic interactions between PAs ( 5 , 6 , 12 , and 13 ; Scheme ) and the siloxy groups of MSNs, − while upconversion nanoparticles can be modified with PAs ( 13 , 14 , and 15 ; Scheme ) via a ligand exchange method and iron oxide NP by EDC coupling (Scheme ). − Another strategy depends on host–guest complexation between nanomaterials ligands and PAs ( 7 , 15 , and 16 ; Scheme ).…”

“…(d) Images of confocal laser scanning microscopy showing the selective accumulation of doxorubicin (DOX) and F16 in mitochondria. Panels c and d reprinted in part with permission from ref . Copyright 2019 John Wiley and Sons.…”

“…Similarly, Jung and co-workers modified 6 @AuNP with a fluorescent ligand (F16) and grafted them onto DOX loaded pyridinium-modified MSN (DOX@PMSN) for mitochondria targeting (F16– 6 @AuNP–DOX@PMSN), forming core–shell-like nanoparticles (Figure c). Then, they studied the uptake via imaging techniques (Figure d) . Drug delivery using nanovalves has been also implemented to promote plant growth.…”

“…Then, they studied the uptake via imaging techniques (Figure 11d). 41 Drug delivery using nanovalves has been also implemented to promote plant growth. (Aminopropyl)triethoxysilane modified Fe agents such as polyamines allowed controlled hormone delivery.…”