Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer

Abstract

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

Keywords: host-guest interactions; nanoassemblies; near-infrared photosensitizers; photodynamic antimicrobials; supramolecular complexes.

Scheme 1

Chemical structures of TTQAd and TTQTMA, and schematic diagram of reversible regulation of antibacterial activity of TTQAd through supramolecular assembly or disassembly.

Figure 1

(a) Absorption spectra of TTQAd and TTQTMA in DMSO and PBS before and after the addition of CB7. (b) Fluorescence spectra of TTQAd and TTQTMA in DMSO and PBS before and after the addition of CB7. (c) Relative changes in the maximum absorbances of TTQAd, TTQTMA, and ICG in PBS irradiated by an 808 nm laser. (d) Changes in the fluorescence intensities of DCFH at 525 nm in the presence of TTQAd, TTQTMA, and ICG under the 808 nm laser before and after the addition of CB7. (e) Changes in the absorbances of ABDA at 380 nm in the presence of TTQAd, TTQTMA, and ICG under the 808 nm laser before and after the addition of CB7. (f) Changes in the fluorescence intensities of SOSG at 525 nm in the presence of TTQAd, TTQTMA, and ICG under the 808 nm laser before and after the addition of CB7.

Figure 2

(a) The ITC isotherms and binding constants of CB7 titrated with TTQAd. (b) The ITC isotherms and binding constants of CB7 titrated with TTQTMA. (c) Diagram of the hydrodynamic diameters of TTQAd and TTQTMA before and after the addition of CB7 (TTQAd/TTQTMA:CB7 = 1:2). (d) Diagram of the zeta potentials of TTQAd and TTQTMA before and after the addition of CB7 (TTQAd/TTQTMA:CB7 = 1:2).

Figure 3

(a) Bacterial viabilities of E. coli and S. aureus treated with TTQAd/TTQTMA (20 μM) in the dark. (b) Bacterial viabilities of E. coli and S. aureus treated with TTQAd/TTQTMA (20 μM) followed by 808 nm laser irradiation (0.5 W cm⁻², 10 min). Different letters (a, b, c, d) in the bar graphs represent significant difference at p < 0.05 levels.

Figure 4

(a,b) Photographs of E. coli colonies on agar plates and bacterial viabilities of E. coli treated with TTQAd or TTQTMA (20 μM) before and after the addition of CB7 (40 μM) with/without 808 nm laser irradiation (0.5 W cm⁻², 10 min). (c,d) Supramolecular switch of the antibacterial efficacy of TTQAd upon the treatment of CB7 and a subsequent treatment of competing guests TMeAd. TTQAd:CB7:TMeAd = 1:2:8. Different letters (a, b, c) in the bar graphs represent significant difference at p < 0.05 levels.

Figure 5

Cell viability after treating with TTQAd (a), TTQTMA (a), TTQAd + CB7 (b), and TTQTMA + CB7 (b) at different concentrations in the absence of light. Cell viability after treating with TTQAd (c), TTQTMA (c), TTQAd + CB7 (d), and TTQTMA + CB7 (d) at different concentrations followed by 808 nm laser irradiation (0.5 W cm⁻²).