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Review
. 2022 Aug 21:21:157-174.
doi: 10.1016/j.bioactmat.2022.08.011. eCollection 2023 Mar.

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

Sathishkumar Gnanasekar  1 , Gopinath Kasi  1 , Xiaodong He  1 , Kai Zhang  1 , Liqun Xu  1   2 , En-Tang Kang  1   3
Affiliations
Review

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

Sathishkumar Gnanasekar et al. Bioact Mater. .

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.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
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
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
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
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
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
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
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
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
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
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
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
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
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.
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