Recent advances in engineered polymeric materials for efficient photodynamic inactivation of bacterial pathogens

Abstract

Nowadays, infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide. Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance (MDR) and limitations with existing therapeutic options. Antibacterial photodynamic therapy (APDT) is a potential therapeutic modality that involves the systematic administration of photosensitizers (PSs), light, and molecular oxygen (O₂) for coping with bacterial infections. Although the existing porphyrin and non-porphyrin PSs were effective in APDT, the poor solubility, limited efficacy against Gram-negative bacteria, and non-specific distribution hinder their clinical applications. Accordingly, to promote the efficiency of conventional PSs, various polymer-driven modification and functionalization strategies have been adopted to engineer multifunctional hybrid phototherapeutics. This review assesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications. Further, the key research findings of the following aspects are considered in-depth with constructive discussions: i) PSs-integrated/functionalized polymeric composites through various molecular interactions; ii) PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated infections; and iii) PSs-embedded films, scaffolds, and hydrogels for regenerative medicine applications.

Keywords: 1O2, Singlet oxygen; APDT, Antibacterial photodynamic therapy; APTT, Antibacterial photothermal therapy; Antibacterial photodynamic therapy; BODIPY, Boron dipyrromethene; BP, Black phosphorus; Biomaterials; CS, Chitosan; CUR, Curcumin; CV, Crystal violet; Ce6, Chlorin e6; Conjugation; HYP, Hypocrellin; Hp, Hematoporphyrin; Hydrogels; ICG, Indocyanine green; MB, Methylene blue; MRSA, Methicillin-resistant Staphylococcus aureus; PCL, Poly(ε-caprolactone); PDA, Polydopamine; PDI, Photodynamic inactivation; PEG, Poly(ethylene glycol); PEI, Polyethylamine; PPIX, Protoporphyrin IX; PSs, Photosensitizers; PVA, Poly(vinyl alcohol); Photosensitizers; Polymers; RB, Rose bengal; ROS, Reactive oxygen species; α-CD, α-cyclodextrin.

Graphical abstract

Fig. 1

(a) Illustration of Type I and Type II photochemical mechanism of APDT (Jablonski diagram). (b) Schematic illustration of the mechanism of bacterial damage. Reprinted with permission from Ref. [8], Copyright © 2020, Elsevier. (c) Schematic illustration of the synthesis of ICG-Ga NPs and their APDT action to treat infected liver abscess. Reprinted with permission from Ref. [51] Copyright © 2021, Elsevier.

Fig. 2

Illustrations of the formation of polymer-PSs composites via different approaches: (a) Preparation of the PS-conjugated pH-responsive supramolecular micelles by host-guest interaction. Reprinted with permission from Ref. [58], Copyright © 2020, American Chemical Society. (b) CMCS-Hp composite conjugated via an amide linkage. Reprinted with permission from Ref. [60], Copyright © 2021, Elsevier. (c) Synthesis route of the PS-conjugated cellulose by covalent incorporation of PPIX and quaternary ammonium salt (QAS). Reprinted with permission from Ref. [62], Copyright © 2019, John Wiley and Sons. (d) Ce6-loading in poly[4-O-(α-d-glucopyranosyl)-d-glucopyranose-modified fluorescence silica NPs. Reprinted with permission from Ref. [65], Copyright © 2019, Springer Nature.

Fig. 3

(a) Schematic of the preparation of CS-Ce6 nanoassembly; (b–d) Flow-cytometry and zeta potential analysis of CS-Ce6 nanoassembly and MRSA mixtures; (e–f)In vitro APDT activity of Ce6 or CS-Ce6 nanoassembly against MRSA and A. baumannii with or without light irradiation. Reprinted with permission from Ref. [61], Copyright © 2019, American Chemical Society.

Fig. 4

(a–b) Schematic of the preparation of Pep@Ce6 micelles via host-guest interaction between PEG-b-polypeptide copolymer and α-CD-Ce6; (c) APDT action of Pep@Ce6 micelles against localized wound infections caused by Pseudomonas aeruginosa (P. aeruginosa); (d) Confocal laser scanning microscopy (CLSM), and (e) transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images of P. aeruginosa treated with phosphate buffered saline (PBS) and Pep@Ce6 micelles with/without light irradiation. Reprinted with permission [59], Copyright © 2021, Elsevier.

Fig. 5

(a) Schematic of the synthesis of Ce6@MnO₂-PEG NPs; (b)Viable bacteria remained in the culture after APDT treatments; (c) Cell proliferation of S. aureus measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay after treatments. Reprinted with permission [86], Copyright © 2020, John Wiley and Sons. (d) Schematic of UCNPs-PVP-RB synthesis and its APDT action; (e) SEM (top) and TEM (bottom) images of XDR-AB after APDT (0–120 min); (f) Cell membrane permeability; (g) Cell membrane integrity of XDR-AB after APDT. Reprinted with permission from Ref. [87], Copyright © 2020, Royal Society of Chemistry.

Fig. 6

(a) Schematic of the preparation of POS-UCNPs/ICG composite and its APDT mechanism; (b) Schematic of POS-UCNPs/ICG induced bacterial damage; (c) Bacterial colonies after treatment with different concentrations of prepared composite; (d) Schematic of POS-UCNPs/ICG triggered anti-inflammation mechanism via CO production. Reprinted with permission [88], Copyright © 2022 Ivyspring International Publisher.

Fig. 7

(a) Schematic of hybrid PDA/Ag₃PO₄/GO-based antibacterial coating on Ti implant. Reprinted with permission [107], Copyright © 2018, American Chemical Society. (b) Schematic of NIR-triggered synergistic antibacterial mechanism of CuFe₂O₄/GO; (c–d) Photographs of S. aureus and E. coli bacterial colonies treated by different samples with/without NIR irradiation; (e–f) The relative antibacterial percentages of S. aureus and E. coli; (g–h) SEM morphologies of bacteria treated with different samples (the red arrows indicate the membrane shrinkages). Reprinted with permission [110], Copyright © 2021, Elsevier.

Fig. 8

(a) Schematic of the preparation of RSNO-loaded PCP hydrogel coating and its photochemical mechanism; (b) Schematic of NIR-induced MRSA biofilm elimination; (c) Schematic of bicinchoninic acid leakage from MRSA after NIR irradiation; (d) Schematic of bone regeneration through M1 polarization of macrophages and MRSA biofilm eradication through gene downregulation. Reprinted with permission [114], Copyright © 2020, American Chemical Society.

Fig. 9

(a) Preparation of the porous PPIX/CA membrane by electrospinning. Reprinted with permission [128], Copyright © 2021, Elsevier. (b) Schematic of the PS- and enzyme-decorated multifunctional nanofiber composite. Reprinted with permission [129], Copyright © 2020, American Chemical Society. (c) Preparation of the CD-functionalized and TPPS-loaded PP fabric and its APDT mechanism. Reprinted with permission [131], Copyright © 2017, American Chemical Society.

Fig. 10

(a) Schematic of CIZPP synthesis and its application; (b and c) Photographs of as-prepared CIZPP electrospun membrane; (d and e) SEM micrographs of CIZPP fibers; (f) NIR- and (b) pH-triggered CUR release profile from CIZPP electrospun membrane. Reprinted with permission [135], Copyright © 2022, Elsevier.

Fig. 11

(a) Schematic of preparation of the CS-BP hydrogel as well as its antibacterial PDI and wound healing mechanisms. Reprinted with permission [140], Copyright © 2018, American Chemical Society. (b) Schematic of the bacteria killing processes with the hybrid CuS-embedded thermo-responsive hydrogel under 808 nm NIR irradiation. Reprinted with permission [142], Copyright © 2018, Royal Society of Chemistry.

Fig. 12

(a) Illustration of the formation of CuS-integrated hydrogel; (b) Self-healing and injectable abilities of the CuS-integrated hydrogel; (c) Cu²⁺ cumulative release from hydrogel into PBS at 37 °C for 60 min with (+) and without (−) 808 nm laser irradiation (n = 3); (d) Photographs of wound area, (e) relative percentage of wound closure, and (f) illustration of wound healing progress after treated with 3 M dressing and CuS-integrated hydrogel. Reprinted with permission [155], Copyright © 2021, Elsevier.

Fig. 13

(a) Schematic diagram of Ag/Ag@AgCl/ZnO hydrogel as a dressing for enhanced antibacterial activity; (b) Swelling behavior of the hydrogels at different pH values; (c)In vivo antibacterial effect of the hydrogel on S. aureus-induced wound infections; (d and e) Bacterial killing efficiency of Ag/Ag@AgCl/ZnO hydrogel against E. coli and S. aureus under simulated sunlight for 20 min (n = 3); (f) The immunology of histological images of the skin tissue samples on rats' wounds after treating with hydrogels and staining with hematoxylin-eosin (H&E). Reprinted with permission [161], Copyright © 2017, American Chemical Society.