Versatile Supramolecular Complex for Targeted Antimicrobial Photodynamic Inactivation

Abstract

We report the development of a supramolecular structure endowed with photosensitizing properties and targeting capability for antimicrobial photodynamic inactivation. Our synthetic strategy uses the tetrameric bacterial protein streptavidin, labeled with the photosensitizer eosin, as the main building block. Biotinylated immunoglobulin G (IgG) from human serum, known to associate with Staphylococcus aureus protein A, was bound to the complex streptavidin–eosin. Fluorescence correlation spectroscopy and fluorescence microscopy demonstrate binding of the complex to S. aureus . Efficient photoinactivation is observed for S. aureus suspensions treated with IgG–streptavidin–eosin at concentrations higher than 0.5 μM and exposed to green light. The proposed strategy offers a flexible platform for targeting a variety of molecules and microbial species.

A Photoactive Supramolecular Complex Targeting PD-L1 Reveals a Weak Correlation between Photoactivation Efficiency and Receptor Expression Levels in Non-Small-Cell Lung Cancer Tumor Models

“…The fluorescence excitation spectrum closely resembles the absorption spectrum of EITC, and no substantial changes in fluorescence emission spectra appear after the binding ( Figure 2 C). Moreover, using eosin in PBS as a reference (Φ F = 0.24 [ 40 ]), we estimated the fluorescence emission quantum yield of the EITC–Atezolizumab complex as 0.11, smaller than the corresponding value for EITC in PBS, for which Φ F = 0.18 [ 31 ]. DOL is most likely too low to explain the observed quenching in terms of the interaction and aggregation between fluorophores.…”

“…The photosensitizing properties of EITC are related to the significant probability of this molecule to undergo an intersystem crossing process, that populates the triplet state with quantum yield Φ T = 0.49 [ 31 ]. Following the time evolution of the ground state bleaching, we estimated that when EITC is bound to Atezolizumab, the triplet quantum yield decreases to 0.20 ± 0.05 (Equation (1)).…”

“…Following the time evolution of the ground state bleaching, we estimated that when EITC is bound to Atezolizumab, the triplet quantum yield decreases to 0.20 ± 0.05 (Equation (1)). This suggests that EITC is probably bound in a region of the protein rich in amino acids able to quench the triplet state of the PS, as observed, for example, for the EITC–streptavidin complex, for which Φ T becomes 0.1 [ 31 ].…”

“…In this work, we propose the use of a photoactive conjugate that consists of the clinical grade PD-L1 binding monoclonal antibody Atezolizumab [ 30 ], covalently linked to the well-known photosensitizer eosin. Photoactive conjugates containing eosin have been recently demonstrated to be effective against bacteria [ 31 , 32 , 33 ] and cancer cells [ 34 ]. The use of this targeting carrier is expected to show a synergic action through photo-induced cancer cell death and the limitation of the mechanisms of tumor cell immune evasion by blocking PD-1/PD-L1 interaction.…”

Adventures in Photodynamic Therapy: Location, Location, Location

“…Another report describes a "supramolecular complex" for use in eradicating microbial infections [14]. It is difficult to deduce the precise procedure used for fabrication of the product.…”