Phototherapy-based combination strategies for bacterial infection treatment

Abstract

The development of nanomedicine is expected to provide an innovative direction for addressing challenges associated with multidrug-resistant (MDR) bacteria. In the past decades, although nanotechnology-based phototherapy has been developed for antimicrobial treatment since it rarely causes bacterial resistance, the clinical application of single-mode phototherapy has been limited due to poor tissue penetration of light sources. Therefore, combinatorial strategies are being developed. In this review, we first summarized the current phototherapy agents, which were classified into two functional categories: organic phototherapy agents (e.g., small molecule photosensitizers, small molecule photosensitizer-loaded nanoparticles and polymer-based photosensitizers) and inorganic phototherapy agents (e.g., carbo-based nanomaterials, metal-based nanomaterials, composite nanomaterials and quantum dots). Then the development of emerging phototherapy-based combinatorial strategies, including combination with chemotherapy, combination with chemodynamic therapy, combination with gas therapy, and multiple combination therapy, are presented and future directions are further discussed. The purpose of this review is to highlight the potential of phototherapy to deal with bacterial infections and to propose that the combination therapy strategy is an effective way to solve the challenges of single-mode phototherapy.

Keywords: Bacterial infection; Combinatorial strategies; Multidrug-resistance; Nanomedicine; Phototherapy.

Figure 1

(A) The mechanism of photodynamic treatment or photothermal treatment activity by phototherapy agent. (B) Combination of different therapies with phototherapy (photodynamic treatment and photothermal treatment), including combination with chemotherapy, combination with chemodynamic therapy, combination with gas therapy and multiple combination therapy.

Figure 2

(A) Constituent elements of Ppa-PLGVRG-Van. Ppa: pyropheophorbide-α, signal molecule; PLGVRG: Pro-Leu-Gly-Val-Arg-Gly, an enzyme-responsive peptide linker; Van: vancomycin, a targeting ligand. (B) Illustration of bacterial infection imaging based on an in vivo aggregation strategy. Copyright 2016, Wiley-VCH.

Figure 3

(A) Schematic illustration of preparation of the nanovehicle (gadofullerene nanoparticles, GFNPs) and (B) killing P. aeruginosa at infected alveoli by photothermal treatment . Copyright 2019, ACS Publications.

Figure 4

(A) The building process of the vancomycin-resistant staphylococcal infection in a murine model and the photodynamic treatment procedure. (B) Bioluminescence images after the treatments with different strategies. (C) Relative bioluminescence intensities and relative bioluminescence areas after each treatment . Copyright 2017, Wiley-VCH.

Figure 5

Schematic illustration of the main synthetic procedure and coordinated antimicrobial strategy of photodynamic treatment and photothermal treatment . Copyright 2020, ACS Publications.

Figure 6

Schematic illustration of the antibacterial mechanism of glycol chitosan conjugated carboxyl graphene (GCS-CG) . Copyright 2018, Elsevier.

Figure 7

Schematic representation of the photothermal conversion of light to heat and the subsequent antimicrobial mechanism taking place. Top right are scanning electron micrographs of E. coli cells before (left) and after (right) treatment with photothermal nanomaterials . Copyright 2018, Wiley-VCH.

Figure 8

Schematic illustration of antibody- conjugated oval-shaped gold nanoparticles to selectively target and destroy pathogenic bacteria . Copyright 2010, Wiley-VCH.

Figure 9

Schematic illustration of 2D reduced graphene oxide supported Au nanostar nanocomposite (rGO/AuNS) triggered antibacterial photothermal lysis . Copyright 2019, ACS publication.

Figure 10

(A) Synthesis roadmap of carbon quantum dots (CQDs) and their appearance as an aqueous suspension under visible and UV light illumination. (B) Concentration and illumination time dependent photodynamic inactivation studies employing CQDs against S. aureus ATCC-6538 and E. coli 8099 . Copyright 2020, Elsevier.

Figure 11

(A)Schematics of NIR-activated thermo-responsive-inspired drug-delivery nanotransporter (TRIDENT) for killing antibiotic-resistant bacteria . Copyright 2019, Nature Publishing Group. (B) Synthetic route of PDA NP-Cip/GC hydrogel and NIR light irradiation-triggered Cip release from PDA NP-Cip/GC hydrogel for bacterial inactivation, Cip: Ciprofloxacin; PDA: Polydopamine; GC: glycol chitosan . Copyright 2019, Elsevier.

Figure 12

(A) Synthetic route of polyethylene glycol functionalized molybdenum disulfide nanoflowers (PEG-MoS₂ NFs). (B) Relative bacteria viabilities of E. coli and B. subtilis after incubation with different conditions without or with NIR irradiation . Copyright 2016, ACS Publications.

Figure 13

(A) Synthetic route of ICG-loaded L-arginine conjugate mesoporous polydopamine nanoparticles (AI-MPDA) . Copyright 2018, Wiley-VCH. (B) The schematic illustration for the preparation of Ce6&CO@FADP, FADP: fluorinated amphiphilic dendritic peptide . Copyright 2020, ACS publication.

Figure 14

(A) Synthetic route of AuAgCu₂O NSs (a hollow gold-silver (AuAg) core and Cu₂O shell). (B) Cumulative release amounts of Ag and Cu ions from AuAgCu₂O NS hydrogel suspension. (C) Representative macroscopic appearance of MRSA-infected full-thickness dorsal cutaneous incisions on BALB/c mice disposed by diverse treatments. Copyright 2020, ACS publications.