Smart Magnetic and Fluorogenic Photosensitizer Nanoassemblies Enable Redox‐Driven Disassembly for Photodynamic Therapy

Abstract

Stimuli-responsive smart photosensitizer (PS) nanoassemblies that allowenhanced delivery and controlled release of PSs are promising for imaging-guided photodynamic therapy(PDT) of tumors.However,the lack of high-sensitivity and spatial-resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo.Herein, we report tumor targeting,r edox-responsive magnetic and fluorogenic PS nanoassemblies (NP-RGD)s ynthesized via self-assembly of acRGD-and disulfide-containing fluorogenic and paramagnetic small molecule (1-RGD)f or fluorescence/ magnetic resonance bimodal imaging-guided tumor PDT. NP-RGD show high r 1 relaxivity but quenched fluorescence and PDT activity;d isulfide reduction by glutathione (GSH) promotes efficient disassembly into as mall-molecule probe (2-RGD)a nd an organic PS (PPa-SH), whichc ould further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors.

Self‐Assembled Porphyrinoids: One‐Component Nanostructured Photomedicines

“…The concentration of GSH in the intracellular matrix is 100‐ to 1000‐fold higher than in extracellular fluids, and the GSH reducing reaction is a common redox system in cancer cells. Self‐assembled nanoparticles endowed with disulphide cross‐linkages may suffer disulfide reduction, triggering disassembly into theranostic – fluorescent and PDT active – PS, as explained in detail below [41,42] . A remarkable example was reported by W. Zhang and coworkers, who reported Pors functionalized with dendritic branches through a disulfide linkage able to self‐assemble into spherical micelles in water [43] .…”

“…Copyright 2015, Wiley‐VCH. B) Proposed self‐assembled structure of NP‐RGD (above); Schematic illustration of NP‐RGD for on demand PDT via activation by intracellular GSH and albumin (middle); Chemical structures of the PPa, DOTA‐Gd chelate, cRGD and a cartoon illustration of HSA structure (below) [41] . Adapted with permission from Ref.…”

“…Self‐assembled nanoparticles endowed with disulphide cross‐linkages may suffer disulfide reduction, triggering disassembly into theranostic – fluorescent and PDT active – PS, as explained in detail below. [ 41 , 42 ] A remarkable example was reported by W. Zhang and coworkers, who reported Pors functionalized with dendritic branches through a disulfide linkage able to self‐assemble into spherical micelles in water. [43] The uptake of these micelles by cells and release of the reduction‐sensitive PS in the cell interior was demonstrated.…”

Smart magnetic resonance imaging-based theranostics for cancer

“…Photosensitiser nanoassemblies (NP-RGDs) have also been reported as GSH and light-responsive dual modal MRI/FL theranostic platforms for PDT 153 . These nanoparticles were prepared via self-assembly of an NIR photosensitiser pheophorbide (PPa) for FL and PDT, a GSH-cleavable linker, a fluorophore to facilitate self-assembly, a paramagnetic Gd-DOTA chelate for MRI and a cyclic RGD peptide for α ν β 3 targeting.…”

Most recent advances on enzyme‐activatable optical probes for bioimaging

“…A large number of optical probes that are activated by other enzymes besides the ones discussed in this review article have appeared in various journals, [ 142–163 ] indicating the rapid development of enzyme‐activatable optical probes and implying that developing biomarker‐activatable probes has emerged as a new direction of research in the fields of chemistry and materials.…”