Controlled Aggregation of a Perylene-Derived Probe for Near-Infrared Fluorescence Imaging and Phototherapy

Abstract

The design and synthesis of water-soluble phototherapeutic agents with near-infrared (NIR) fluorescence emission is highly desirable for cancer diagnosis and treatment. Here, we report the construction of an amphiphilic perylene-derived photosensitizer, AP. AP shows NIR emission with large Stokes shift (130 nm) and high 1O2 quantum yield (22%). It can self-assemble into nanoparticles in aqueous solution with quenched fluorescence emission due to aggregation-induced quenching. Upon membrane anchoring, AP is able to disassemble into free monomer molecules and specifically “light up” the cell membrane without the usually required washing procedures. Furthermore, AP is subsequently used for the efficient photodynamic therapy against cancer cells and solid tumors. The in vitro and in vivo experiments clearly indicate that AP is suitable for biological imaging and can serve as a promising photosensitizer for tumor suppression.

Molecular Engineering of Near-Infrared Fluorescent Probes for Cell Membrane Imaging

“…By modifying the structure of perylene molecule, a washing-free CM staining NIR probe will be constructed based on disassembly light-up fluorescence strategy. For example, in 2021, Yu et al developed an amphiphilic NIR perylene derivative (probe 12 ) with a hydrophilic quaternary ammonium functional group and a hydrophobic long alkyl chain ( Figure 12 A) [ 69 ]. In aqueous solution, this probe could self-assemble into nanoparticles without fluorescence emission.…”

“…( E ) Tumor volume changes of the 4T1 tumor-bearing mice under different treatments. Copyright 2021 American Chemical Society [ 69 ].…”

Aggregation-Induced Emission Luminogens for Enhanced Photodynamic Therapy: From Organelle Targeting to Tumor Targeting

“…Yang et al reported an amphiphilic perylene derivative AIE-PSs named AP ( ϕ Δ = 0.22, methylene blue as reference) which is capable of cell-membrane-targeting [ 44 ]. AP could form nanoparticles by self-assembly in an aqueous solution and decompose into free monomeric molecules after membrane anchoring ( Figure 4 ).…”

Photosensitive Chitosan-Based Injectable Hydrogel Chemically Cross-Linked by Perylene Bisimide Dopamine with Robust Antioxidant and Cytotoxicity Enhancer Properties for In Vitro Photodynamic Therapy of Breast Cancer

“…Perylene diimide (PDI) derivatives exhibited tremendous potential as a PS in PDT applications due to their excellent thermal and photostability, high extinction coefficients, low dark toxicity, and significant singlet oxygen quantum yield. , Structurally, PDI is a rigid hydrophobic aromatic polycyclic molecule, and its π–π aggregation has limited its biological application. , Interestingly, by conjugating PDIs with biological molecules such as amino acids and short peptide sequences, soluble structures are created with unique optical, physicochemical, and structural properties, which could modulate the self-assembly of PDI for different biomedical applications. − Several groups have reported using conjugated PDI derivatives due to their stability, phototoxicity, and biocompatibility properties in PDT …”

“…29−31 Several groups have reported using con-jugated PDI derivatives due to their stability, phototoxicity, and biocompatibility properties in PDT. 32 Hydrogels have received increasing attention as promising nonimmunogenic delivery vehicles for enhancing the biological activity of PSs in PDT with the inherent exclusive characteristics of low toxicity, biodegradability, hydrophilic matrix, and drug-local and controlled diffusion properties. 33,34 Hydrogels are three-dimensional (3D) cross-linking hydrophilic polymer chains that absorb significant amounts of water while maintaining self-organization.…”