Carbon Dots in Photodynamic/Photothermal Antimicrobial Therapy

Abstract

Antimicrobial resistance (AMR) presents an escalating global challenge as conventional antibiotic treatments become less effective. In response, photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged as promising alternatives. While rooted in ancient practices, these methods have evolved with modern innovations, particularly through the integration of lasers, refining their efficacy. PDT harnesses photosensitizers to generate reactive oxygen species (ROS), which are detrimental to microbial cells, whereas PTT relies on heat to induce cellular damage. The key to their effectiveness lies in the utilization of photosensitizers, especially when integrated into nano- or micron-scale supports, which amplify ROS production and enhance antimicrobial activity. Over the last decade, carbon dots (CDs) have emerged as a highly promising nanomaterial, attracting increasing attention owing to their distinctive properties and versatile applications, including PDT and PTT. They can not only function as photosensitizers, but also synergistically combine with other photosensitizers to enhance overall efficacy. This review explores the recent advancements in CDs, underscoring their significance and potential in reshaping advanced antimicrobial therapeutics.

Keywords: antimicrobial; carbon dots; nanoparticles; photodynamic therapy; photosensitizers; photothermal therapy.

Figure 2

(a) Schematic representation of the synthesis of citric acid-derived carbon dots (C-DOTS) and in vivo and in vitro antibacterial photodynamic therapeutic studies. Photoexcited C-DOTS reduced the number of bacterial colonies (log CFU/mL) based on the light dose 450 nm, 40 mW/cm² delivered [135]. (b) Synthesis of red-carbon dots (R-CDs) by solvothermal method and its dual effect of intrinsically antibacterial and photodynamic antibacterial effect against MRAB and biofilms [140].

Figure 1

Schematic illustration of three types of mechanisms in photodynamic therapy (PDT) including a series of potential energy transfer processes that occur in photosensitizers after light excitation (Jablonski diagram), along with possible photodynamic therapy mechanisms (with (Type I and Type II) or without oxygen (Type III)) that may take place during this process. The Jablonski diagram illustrates the electronic states of a molecule, including the ground state (S₀), singlet excited states (S₁, S₂, S_n), and triplet states (T₁). Upon absorption of a photon, electrons are excited from S₀ to higher singlet states (S₁, S₂, Sn). Fluorescence occurs when electrons return from an excited singlet state (S₁) to the ground state (S₀). Intersystem crossing (ISC) is a non-radiative transition from a singlet state (S₁) to a triplet state (T₁). Phosphorescence involves the emission of a photon when electrons return from a triplet state (T₁) to the ground state (S₀). Internal conversion (IC) represents non-radiative transitions between singlet states (e.g., S_n to S₁) [40,41].

Figure 3

(a) Photodynamic efficiency of amine-functionalized CDs (CDs-NH₂) for the inactivation of E. coli upon irradiation at 0.3 W for 10 min and 20 min [143]. (b) Influence of the CDs-NH₂ and CDs-AMP concentration on the treatment efficiency of E. coli without (solid lines) and with (dash lines) visible light illumination (20 min, 0.3 W). The error bars represent the standard deviation of three independent experiments [143]. (c) Scheme for synthesis of BSA-coated CDs (BSA-CD) for visible-light-induced ROS generation and simultaneous release of ciprofloxacin for antibacterial activity [144]. (d) Percentage cell survival of S. aureus in the presence of BSA-CD loaded with ciprofloxacin. Percentage cell survival of E. coli in the presence of BSA-CD loaded with ciprofloxacin [144]. Data were considered statistically significant and highly significant when p < 0.05 and p < 0.001, respectively (**, 0.05 < p < 0.01; ***, 0.01 < p < 0.001).

Figure 4

(a) Synthetic routes of ZnPc-CQDs for PDT/PTT antibacterial effects [146]. (b) Bacterial viability after treatment with different concentrations of ZnPc-CQDs with and without irradiation [146]. (c) CDs-MR synthesis scheme with its cell penetration and antimicrobial photoactivation [147]. (d) Disk-diffusion (Kirby–Bauer) tests of the antimicrobial activity of CD-MR (120 μg) on MHA plates against C. albicans, C. neoformans, and S. aureus [147].

Figure 5

(a) Fabrication of PAN-CQDs NFs and the photodynamic inactivation of bacteria upon visible light illumination [157]. (b) Photodynamic inactivation studies employing PAN-CQDs NFs against Gram-negative bacteria E. coli and P. aeruginosa as well as Gram-positive bacteria S. aureus and B. subtilis. Displayed is the survival rate for the PAN-CQDs-2.5% NFs dark control (dark grey bar) and illuminated PAN NFs light control (red bar) conditions, blue and green bars represent the PAN-CQDs NFs (0.6 and 2.5%) against bacteria, respectively. Studies were performed with a 60 min dark pre-incubation followed by 90 min illumination [157]. (c) Design of CS/nHA/CDs scaffolds for enhancing BMSC adhesion and differentiation, promoting vascularized new bone formation, tumor ablation, and bacterial eradication by PTT [158]. (d) Number of clinically relevant S. aureus (top) and E. coli (bottom) bacterial colonies after bacteria from the harvested samples were cultured for 24 h after 1-week treatments in vivo. Each value is the mean ± standard deviation; * p < 0.05, ** p < 0.01 [158].

Figure 6

(a) Synthesis of the CDs/Cur nanocomposite and bactericidal activities of CDs/Cur upon dual wavelength (405 + 808 nm) illumination [36]. (b) Agar plate photographs of E. coli treated with Cur or CDs/Cur, respectively, were taken under (non) light irradiation conditions. The corresponding dependence of E. coli survival fraction on the concentration of Cur and CDs/Cur was measured, respectively, under non-light, 405 nm light, and 405 + 808 nm light. Values are means ± standard deviation (SD) (n = 3) [36]. (c) Design of hybrid hydrogel derived from carbon dots (CDs), protoporphyrin IX (PpIX), and DNA [37]. (d) Plate count assay for S. aureus. cell survival with CD-DNA-PpIX hydrogel (PpIX:1 mM) exposed to UV light [37]. Each value is the mean ± standard deviation; *** p < 0.001, ns: non-significant.