Pillar[5]arene-Based Switched Supramolecular Photosensitizer for Self-Amplified and pH-Activated Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) has emerged as a promising and spatiotemporally controllable cancer treatment modality. However, serious skin photosensitization during the PDT process limits the clinical application of PDT. Thus, the construction of “smart” and multifunctional photosensitizers has attracted substantial interest. Herein, we develop a mitochondria-targeting and pH-switched hybrid supramolecular photosensitizer by the host–guest interaction. The PDT efficacy of supramolecular photosensitizers can be quenched by the Förster resonance energy transfer (FRET) effect during long circulation and activated by the dissociation of supramolecular photosensitizers in an acidic tumor microenvironment, benefitting from the dynamic feature of the host–guest interaction and pH responsiveness of the water-soluble pillar[5]­arene on gold nanoparticles. The rational integration of mitochondria-targeting and reductive glutathione (GSH) elimination in the hybrid switchable supramolecular photosensitizer prolongs the lifetime of reactive oxygen species generated in the PDT near mitochondria and further amplifies the PDT efficacy. Thus, the facile and versatile construction of switchable supramolecular photosensitizer offers not only the targeted and precise phototherapy but also high therapeutic efficacy, which would provide a new path for the clinic application of PDT.

A carboxylatopillar[5]arene-based pH-triggering supramolecular photosensitizer for enhanced photodynamic antibacterial efficacy

“…To obtain an acid-triggering antibacterial photosensitizer, a porphyrin derivative with four quaternary ammonium groups (TPyP) was first synthesized according to the previous report. 16 The detailed synthetic processes are presented in Scheme S1 (ESI†) and the 1 H NMR spectrum confirmed that TPyP was successfully synthesized (Fig. S1, ESI†).…”

“…For the assembled process, there are two main interactions (host–guest and electrostatic interaction) between AgTPyP with four quaternary ammonium groups and pillar[5]arene (P[5]) with ten negative carboxylic acid groups to eventually drive the formation of nanoparticles with a diameter of around 212 nm. 16 Additionally, the acid-triggered feature of AgTPyP@P[5] was characterized by ζ-potential measurements in Fig. 1d.…”

A Nanotheranostic System Combining Lysosomal Cell Death and Nuclear Apoptosis Functions for Synergistic Cancer Therapy and Addressing Drug Resistance

“…As is well known, mitochondrial dysfunction results in the decrease in mitochondrial membrane potential, leading to the transformation of the aggregation of JC‐1 (red fluorescence) into monomers (green fluorescence). [ 44,45 ] As displayed in Figure 1E and Figure S13, Supporting Information, compared with that of the control group (Control), the weaker green fluorescence and brighter red fluorescence were found in 4T1 cells cultured by TM, while a contrary phenomenon was displayed in cells cultured by Carbonyl cyanide 3‐chlorophenylhydrazone (CCCP) or DOX, showing brighter green fluorescence and weaker red fluorescence. The fluorescence intensity presented a conspicuous difference between TM and DOX cultured cells (Figure S14, Supporting Information).…”

DNA nanolantern as biocompatible drug carrier for simple preparation of a porphyrin/G-quadruplex nanocomposite photosensitizer with high photodynamic efficacy

“…The Q-band absorption at around 650 nm is also used in some reports. [69][70][71][72][73] However, the poor light absorption capability at this wavelength will inevitably weaken the PDT efficiency. Our cationic porphyrin TMPipEOPP (Scheme S1, ESI †) can specifically bind to the DNA G-quadruplex (e.g., KRAS), resulting in the redshift of the Soret band from 421 nm to 454 nm, accompanied by the emergence of a strong light absorption at around 692 nm.…”