Metalloporphyrin-based photosensitizers are porphyrin ring compounds in which the introduction of metal ions (such as zinc, aluminum, or ruthenium) enhances their photosensitizing properties (Hlabangwane et al., 2023). Pujari et al. coupled metal porphyrins to lignin-based zinc oxide to develop hydrophilic nanoconjugates that showed significantly improved PDT efficiency when treating bacterial infections under dual light irradiation (Figure 1A) (Pujari et al., 2024). The nanoconjugates showed the highest fluorescence intensity when exposed to dual light (UV and green light) and exhibited high bactericidal activity due to increased ROS generation capacity (Figure 1B). In addition, the results of nucleic acid leakage experiments showed that the nanoconjugates resulted in more DNA leakage under dual light irradiation compared to single light irradiation, further supporting their ROS generation efficiency. The overall findings showed that the nanoconjugates had a destructive effect on microbial cells through the ROS produced by PDT, thereby achieving an effective antibacterial effect (Figure 1C).

These photosensitizers absorb light, particularly in the visible range (400–700 nm), making them highly effective for PDT applications (Abbas et al., 2023). Upon light exposure, metalloporphyrins transfer energy to surrounding oxygen molecules, producing singlet oxygen and other ROS (Bi et al., 2023). These reactive species have strong oxidizing properties and are capable of destroying bacterial cell walls, cell membranes, and critical intracellular components, including proteins and nucleic acids, to achieve an antimicrobial effect (Kumar et al., 2023).

Metalloporphyrin photosensitizers demonstrate broad-spectrum antimicrobial activity, especially against drug-resistant strains (Michalska et al., 2022). Zinc (II) porphyrin (ZnP), for instance, has been proven to be effective in killing bacteria, such as MRSA, Escherichia coli, and Pseudomonas aeruginosa. Studies have shown that ZnP, when irradiated, generates ROS that significantly damage bacterial cell membranes, leading to the leakage of intracellular contents and subsequent bacterial death (Nejad et al., 2022).

Biofilm infections, characterized by a complex extracellular polymer matrix that shields bacteria from antibiotics and immune system attacks, pose a major challenge in chronic infections. Metalloporphyrin photosensitizers offer promising solutions against biofilms (Pucelik et al., 2024). Aluminum phthalocyanine chloride (AlPcCl), for example, has demonstrated excellent photosensitizing efficacy against Pseudomonas aeruginosa biofilms. Upon light exposure, AlPcCl penetrates the biofilm and generates ROS, killing greater than 90% of the embedded bacteria (Souza et al., 2022).

While the antimicrobial efficacy of metalloporphyrin photosensitizers has been well documented in both laboratory and animal models, their clinical application remains in the early stages (Zhang et al., 2023). Preclinical studies suggest promising therapeutic outcomes for superficial bacterial infections, such as skin infections, postoperative wound infections, and periodontal diseases (Castillo et al., 2024). Notably, zinc porphyrin-based PDT significantly reduced bacterial loads and accelerated wound healing in MRSA-infected skin models.

However, some limitations must be addressed. Metalloporphyrin photosensitizers typically require visible light for activation, limiting their penetration into deeper tissues and reducing their efficacy in treating deep-seated infections. Additionally, the success of PDT depends on adequate oxygen supply to tissues, and hypoxic environments, such as those of deep infections or abscesses, may reduce treatment effectiveness. Though metalloporphyrin photosensitizers have demonstrated good safety profiles in in vitro and animal studies, their long-term safety and metabolic pathways in humans require further research.

Future efforts should focus on molecular modification and functional design to enhance the light absorption properties and ROS generation by metalloporphyrin photosensitizers. Combining these photosensitizers with other antimicrobial technologies could further improve their efficacy, positioning metalloporphyrin-based PDT as a valuable tool in fighting drug-resistant bacterial infections.

Organic small-molecule photosensitizers are compounds with relatively low molecular weight and diverse structures, offering significant advantages in antibacterial therapy (Atac et al., 2024). Their structural versatility and efficient photosensitization properties make them ideal candidates for antimicrobial applications. Due to their simpler molecular structures and ease of synthesis, organic small-molecule photosensitizers can be functionally modified to enhance their photosensitizing performance, broaden their light absorption range, and improve their biocompatibility (Gill et al., 2022). These properties contribute to their effectiveness against a variety of pathogens, including Gram-positive bacteria, Gram-negative bacteria, and fungi, with particular success in combating drug-resistant strains like MRSA and VRE (Gong et al., 2024).

Atac et al. studied Cl-Hem, an organic small-molecule photosensitizer, and explored its bactericidal effect (Figure 2A) (Atac et al., 2024). Dose-dependent antibacterial effects were verified in plankcells and biofilms of Gram-positive bacteria with and without 640-nm laser irradiation (Figure 2B). Based on the characteristic green fluorescence of the ROS sensor (Figures 2C, D), a significant increase (73%) in Streptococcus epidermalis killing was observed at 50 μg/mL of Cl-Hem 20 min after laser irradiation (p < 0.0001). Interestingly, this dose of Cl-Hem also resulted in a 30% increase in ROS in the absence of laser irradiation (p = 0.0016). However, no antibacterial effect was observed without laser irradiation, indicating that photoinduced toxicity was the main source of antibacterial activity. Although Cl-Hem produced some amount of ROS in the absence of light, its concentration and reactivity were not sufficient to cause significant bacterial damage. In contrast, ROS production under light exposure was higher and more active enough to trigger the destruction of bacterial cell membranes and cellular structures to achieve effective bactericidal effects.

One of the key advantages of certain organic small-molecule photosensitizers is their absorption capacity in the near-infrared (NIR) range, which allows deeper tissue penetration and the ability to treat infections that reside in deeper tissue layers (Hao et al., 2024). For example, indocyanine green (ICG), a widely used cyanine dye, absorbs light at approximately 808 nm and has been shown to be particularly effective in PDT for deep tissue infections (Liu X. et al., 2022).

The photosensitization mechanism of these organic small molecules typically involves excitation under specific wavelengths of light, transitioning them from a singlet state to a triplet state where they transfer energy to oxygen molecules. This energy transfer produces ROS, such as singlet oxygen, which cause oxidative damage to bacterial cell membranes, proteins, and DNA, eventually leading to bacterial death.

ICG is one of the most extensively studied cyanine dye photosensitizers due to its excellent NIRabsorption properties and strong tissue penetration. Studies have demonstrated ICG’s ability to effectively kill a variety of pathogenic bacteria, including MRSA, Escherichia coli (Xiong et al., 2024), and Pseudomonas aeruginosa, under light irradiation. For example, in one study, ICG significantly promoted wound healing in MRSA-infected wounds following near-infrared irradiation. This makes ICG particularly suitable for treating recalcitrant infections, such as infections following skin injuries and post-surgical infections.

Rhodamine B, a photosensitizer commonly used for cell labeling and fluorescent probes, has shown great potential for antimicrobial PDT. Studies indicate that rhodamine-type photosensitizers generate ROS under light irradiation, effectively killing both Gram-positive and Gram-negative bacteria (Yan Y. et al., 2023). For instance, in one experiment, rhodamine B demonstrated a bactericidal rate of over 90% against MRSA and 85% against Pseudomonas aeruginosa, while also inhibiting biofilm formation (Xue et al., 2023). Its straightforward structure, high stability, and ease of synthesis and modification make rhodamine B a promising candidate for multifunctional antimicrobial materials.

Coumarin-based photosensitizers are known for their wide light absorption range and ability to generate ROS in the UV-visible range (Xiong et al., 2024). Although less frequently studied in antimicrobial PDT, coumarin photosensitizers have been shown to kill Gram-positive and Gram-negative bacteria after photosensitization. In one study, coumarin photosensitizers effectively disrupted the cell membranes of Escherichia coli and MRSA, increasing cell membrane permeability and accelerating bacterial death (Ma M. et al., 2024).

Organic small molecule photosensitizers have broad-spectrum antimicrobial activity, particularly against drug-resistant strains and biofilm-associated infections. However, certain limitations must be addressed. These include the need for specific light sources, potential problems with photostability, and phototoxicity concerns. To overcome these challenges, future research should focus on modifying the molecular structure of these photosensitizers to improve their properties, incorporating nanotechnology, and developing combination therapy strategies.

Through continued innovation and optimization, organic small-molecule photosensitizers hold promise for becoming more effective tools in combating bacterial infections, particularly in clinical settings.

Polymer-based photosensitizers are composite materials that integrate photosensitizers with polymer matrices, typically through covalent bonds or non-covalent interactions (Ahmetali et al., 2023). The polymer matrix, which may be composed of natural or synthetic materials, enhances the stability, biocompatibility, and sustained release of the photosensitizer at the infection site (Bryaskova et al., 2023). This design reduces the non-specific aggregation of photosensitizers in vivo, ensuring more targeted and efficient antimicrobial effects. The underlying mechanism remains consistent with that of traditional PDT, where ROS are generated upon light irradiation, leading to bacterial cell membrane damage and cell death (Chen et al., 2024).

Common polymer materials used in such composites include polyethylene glycol (PEG), chitosan, and polylactic-co-glycolic acid (PLGA). These polymers not only improve the biological stability of the photosensitizers but also allow for controlled release, making them highly effective in clinical applications (Elian et al., 2024).

Incorporating porphyrin-based photosensitizers into polymer matrices significantly improves their biostability and antimicrobial efficacy in vivo. For example, porphyrin photosensitizers combined with PEG have demonstrated enhanced photosensitization and increased antimicrobial activity under light irradiation (Hino et al., 2024). Studies have shown that such composites effectively kill MRSA and Escherichia coli with a sterilization rate exceeding 95% (Jiao et al., 2022). Additionally, these polymer-porphyrin complexes have been developed into antimicrobial coatings, such as those used in wound dressings and on medical implant surfaces. These coatings continuously release ROS, preventing bacterial infections at wound sites (Liang et al., 2022).

Chitosan, a naturally derived polymer with intrinsic antimicrobial properties and excellent biocompatibility, has been widely applied in wound dressings, biomedical implants, and antimicrobial coatings (Ma Z. et al., 2024). When combined with photosensitizers, chitosan significantly enhances their antimicrobial effect while also providing long-lasting antibacterial activity. Chitosan-based photosensitizers have shown great promise, particularly in antimicrobial wound dressings (Manathanath et al., 2024). Research has demonstrated that the combination of chitosan with porphyrin photosensitizers improves bactericidal efficiency at infection sites under light exposure, showing potent effects against drug-resistant bacteria, including MRSA (Qian et al., 2024).

Cyanine dyes, such as ICG, have gained widespread attention for their excellent light absorption properties in the NIR region (Wang et al., 2022). When combined with polymeric materials, cyanine dye-based photosensitizers exhibit enhanced stability and antimicrobial efficacy. For example, composites of ICG and PEG significantly improve the production of ROS under NIR light, effectively killing MRSA and E. coli in deep tissue infections. These composites are particularly advantageous for treating infections that are difficult to cure by conventional antimicrobial methods (Xu et al., 2022).

Titanium dioxide (TiO₂) is a well-known photocatalytic material that is often used as an antimicrobial agent when combined with polymers (Tsai et al., 2024). Polymer-based TiO₂ photosensitizers are not only effective in antimicrobial coatings but also widely used in water treatment and environmental applications. For example, PLGA combined with TiO₂ has demonstrated high efficacy in killing environmental bacteria, such as E. coli and MRSA, upon light irradiation (Zhou et al., 2024).

The application of polymer-based photosensitizers has great potential, especially in combating biofilm infections and developing long-lasting antimicrobial materials. Embedding photosensitizers into polymer matrices greatly enhances their biocompatibility and stability, ensuring efficient antimicrobial activity in vivo.

However, certain challenges remain. These include limited light penetration, potential material degradation, and the complexity of synthesizing polymer-based photosensitizers. Future research should focus on optimizing the combination of photosensitizers with polymer matrices to improve antimicrobial efficacy. Developing low-cost, biodegradable, and efficient polymer-based photosensitizers could further promote their use in clinical settings.

Metallic nanomaterials have emerged as a research hotspot due to their excellent photothermal conversion efficiency, biocompatibility, and potent bactericidal effects against a wide range of pathogens (Ahmad and Ansari, 2022). These agents absorb specific wavelengths of light (typically in the NIR range) and convert this energy into heat, raising local temperatures to 40°C–60°C, which disrupts bacterial cell membranes, walls, and proteins, ultimately leading to cell death (Amarasekara et al., 2024). Common metallic nanomaterials used in PTT include gold, silver, copper, palladium, and ruthenium nanoparticles (Dediu et al., 2023).

Despite its many advantages, the clinical applicability of PTT as the sole sterilization strategy is hampered by the necessity of higher temperatures that can potentially harm healthy tissues (Ding et al., 2022). To overcome this challenge, Wang et al. introduced antimicrobial peptides (AMPs) to modify the surface of gallium-based liquid metal (LM) nanoantibacterial agents, thereby enhancing their photothermal antibacterial effects at lower temperatures (Figures 3A, B) (Wang B. et al., 2024). Although LM nanoparticles exhibit some antibacterial properties, their bactericidal effect is relatively limited. The researchers demonstrated a notable reduction in the number of bacteria after 808 nm NIR laser irradiation, thereby showing that their method significantly enhanced the antibacterial ability of the material system (Figures 3C, D).

Gold nanoparticles (AuNPs), particularly gold nanorods (GNRs), are widely used in antimicrobial research due to their efficient photothermal conversion at NIR wavelengths (808 nm) (Doveri et al., 2023). Under light irradiation, GNRs rapidly elevate the temperature to 60 °C, which is sufficient to disrupt bacterial cell membranes (Gu et al., 2023). Studies have demonstrated that GNRs achieve over 95% bactericidal rates against MRSA and Escherichia coli (Hajfathalian, 2022). In combination with antibiotics, GNRs significantly enhance the efficacy of antimicrobial treatments against multidrug-resistant bacteria like MRSA (Hajfathalian, 2024). Additionally, AuNPs have been incorporated into medical dressings to treat chronic wound infections, significantly accelerating wound healing (Ilhami et al., 2023).

Silver nanoparticles (AgNps) exhibit broad-spectrum antimicrobial properties in addition to their excellent photothermal effects. When exposed to light, AgNPs rapidly heat up and disrupt bacterial membranes (Joudeh et al., 2022). The release of silver ions (Ag+) further inhibits bacterial growth by interacting with bacterial proteins and DNA (Li X. et al., 2024). In one study, AgNPs successfully eradicated over 99% of MRSA when used for PTT (Lin et al., 2022). These nanoparticles are also used as nanocarriers for antibiotics, enhancing targeted delivery and antimicrobial efficacy (Ma et al., 2022). AgNP-coated medical devices, such as catheters and implants, prevent bacterial infections and biofilm formation through their combined photothermal and antimicrobial properties (Liu et al., 2023).

Copper nanoparticles have garnered attention for their cost-effectiveness and high photothermal conversion efficiency. CuNPs have demonstrated potent bactericidal effects against both Gram-positive and Gram-negative bacteria, including MRSA and E. coli (Mammari and Duval, 2023). In one study, CuNPs achieved a 97% killing rate of MRSA in biofilm environments. However, the biosafety of copper nanoparticles remains a concern, as excessive copper accumulation in vivo may trigger oxidative stress and damage host cells (Manivasagan et al., 2024).

Palladium and ruthenium nanoparticles are being explored for their multifunctional properties in antimicrobial applications (Miao et al., 2024). In addition to their photothermal effects, these nanoparticles catalyze the production of ROS, further enhancing their antimicrobial effect (Mutalik et al., 2022). Palladium nanoparticles have been shown to kill Pseudomonas aeruginosa and MRSA with broad-spectrum activity, demonstrating their potential in tackling resistant bacterial infections (Naskar and Kim, 2022).

Metallic nanomaterials have shown tremendous potential in addressing the challenge of bacterial resistance. Gold, silver, and copper nanoparticles, in particular, offer multiple mechanisms for combating bacterial infections, including direct photothermal damage and synergistic effects with other antimicrobial methods (Pang Q. et al., 2023; Sethulekshmi et al., 2022; Sharma and Arnusch, 2022). However, challenges such as potential toxicity, limited light penetration in vivo, and the metabolic pathways of these materials require further investigation. Future research should focus on optimizing nanoparticle design, developing intelligent delivery systems, and conducting clinical studies to assess the safety and efficacy of these photothermal agents. Metallic nanomaterials could become a critical tool in treating multidrug-resistant bacterial infections, especially those involving biofilms.

Carbon-based materials possess unique structural and physicochemical properties that allow them to efficiently convert light energy into heat, thereby killing bacteria (Balou et al., 2022). Common carbon-based photothermal agents include graphene and its derivatives, CNTs, carbon quantum dots (CQDs), and fullerenes (Dediu et al., 2023).

Geng et al. synthesized high graphidic acid N-doped graphene quantum dots (N-GQD) with efficient NIR-II photothermal conversion properties for photothermal antibacterial therapy (Figures 4A, B) (Geng et al., 2022). The obtained N-GQDs showed strong NIR absorption in the range of 700–1,200 nm and achieved high photothermal conversion efficiencies of 77.8% and 50.4% at 808 and 1,064 nm, respectively. In the presence of 808 or 1,064 nm laser, N-GQD achieved excellent antibacterial and anti-biofilm activity against MDR bacteria (methicillin-resistant MRSA, MRSA) (Figure 4C). In vivo studies confirmed that hyperthermia generated by N-GQD plus NIR-II laser antagonized MDR bacterial infection and thereby significantly accelerated wound healing.

Graphene oxide (GO), with its two-dimensional structure and high photothermal conversion efficiency, is widely used in antimicrobial research. When exposed to NIR light (808 nm), GO generates localized high temperatures that kill bacteria (Chao et al., 2023). Additionally, GO itself possesses intrinsic antibacterial activity, physically disrupting bacterial cell membranes and inducing oxidative stress. Studies have shown that GO achieves a sterilization rate of 90% against MRSA and E. coli in PTT applications, and it penetrates and destroys biofilms, significantly enhancing the effectiveness of PTT (Chu et al., 2022).

Both single-walled and multi-walled CNTs (SWCNTs and MWCNTs) have high specific surface areas and light absorption capacities, making them effective in generating heat for PTT (Demirel et al., 2022). Under NIR light, CNTs raise local temperatures to 50°C–60°C, which is sufficient to kill pathogenic bacteria (Dong et al., 2023). CNTs may also be combined with other antimicrobial agents, such as AgNps or antibiotics, to form multifunctional composites that enhance their antimicrobial effects. In one study, SWCNTs effectively killed MRSA and E. coli under light exposure while also disrupting biofilm structures (Fang M. et al., 2023).

CQDs have gained significant attention in antimicrobial applications due to their nanometer size, excellent photothermal conversion efficiency, and biocompatibility (Feng et al., 2024). CQDs generate heat upon light absorption and also be designed to target specific bacterial infections. Studies have shown that CQDs are effective in killing Pseudomonas aeruginosa and MRSA, demonstrating their broad-spectrum antimicrobial activity. CQDs are also suitable for coating wound dressings and medical devices to prevent infections (Geng et al., 2022).

Fullerenes and their derivatives, with their unique cage-like structures, show potential in PDT (Hu et al., 2024a). Fullerenes efficiently generate heat under light irradiation and can be combined with photosensitizers to enhance PDT, creating a dual antimicrobial mechanism. In one study, fullerenes combined with AgNps effectively killed MRSA and E. coli under light exposure, demonstrating synergistic effects (Huo et al., 2024).

Carbon-based materials, such as graphene, CNTs, CQDs, and fullerenes, have shown great promise in antimicrobial PTT due to their efficient photothermal conversion properties and broad-spectrum activity (Jiang et al., 2024). However, challenges related to light penetration, biosafety, and the complexity of the material preparation process remain barriers to clinical translation (Lagos et al., 2023). Future research should focus on developing more efficient, safe, and easily producible carbon-based materials, integrating them with other antimicrobial agents and delivery systems. With continued optimization and clinical validation, carbon-based photothermal agents could become a vital tool in the fight against drug-resistant bacterial infections.

Polymer-based photothermal agents are composite materials formed by integrating polymer matrices with photothermally active substances, such as metallic nanoparticles, carbon nanomaterials, or organic dyes (Bayan et al., 2024). These polymers, which may be natural or synthetic, enhance the biocompatibility, stability, and functionality of photothermal agents (Fang Z. et al., 2023). Polymer-based materials not only improve the overall safety profile of PTT but also allow for controlled release and targeted delivery of photothermal agents, making them effective in clinical antimicrobial applications (Hu et al., 2024a).

Metallic nanoparticles like gold, silver, and copper exhibit excellent photothermal conversion efficiency and are often combined with polymer matrices to enhance their biocompatibility and antimicrobial efficacy (Li J. et al., 2024).

For example, AuNPs combined with PEG have demonstrated strong antimicrobial properties (Li J. et al., 2023). In one study, the gold nanoparticle-PEG composite effectively killed MRSA and Escherichia coli under NIR light (808 nm) irradiation, achieving a sterilization rate exceeding 95% (Ghayyem et al., 2022). The PEG coating enhances the stability of the AuNPs and minimizes their aggregation, making this composite material suitable for clinical applications such as wound dressings or implant coatings.

Similarly, AgNps show enhanced antimicrobial activity when combined with the naturally derived polymer chitosan (Luo Y. et al., 2022). This composite material has demonstrated potent bactericidal effects, particularly against multidrug-resistant bacteria like MRSA (Mei et al., 2024). Chitosan-based AgNp coatings have been applied to medical devices, such as urinary catheters and implants, to prevent bacterial infections and biofilm formation (Qi et al., 2022).

Carbon-based materials, such as CNTs and graphene, have high photothermal conversion efficiencies and, when integrated with polymer matrices, create multifunctional composites with potent antimicrobial properties (Ren et al., 2023).

For example, a composite material formed by combining CNTs with polypyrrole (PPy) has shown significant bactericidal effects against MRSA and E. coli under NIR light irradiation (Wang L. et al., 2023). Studies have indicated that the local temperature of this composite material reaches up to 60 °C upon light exposure, which is sufficient to damage bacterial cell membranes and cause cell death (Wang X. et al., 2024).

Graphene exhibits excellent antimicrobial activity when combined with chitosan, particularly in fighting biofilm-associated infections (Wu et al., 2023). The graphene-chitosan composite has demonstrated strong bactericidal effects against both Gram-positive and Gram-negative bacteria, with enhanced penetration and destruction of biofilms (Zhang et al., 2024).

Organic dyes, such as ICG and phthalocyanine dyes, are widely used in PTT due to their efficient light absorption and photothermal conversion properties (Zhao et al., 2023). When combined with polymer matrices, these dyes exhibit improved stability and enhanced antimicrobial effects, especially in deep tissue infections.

For instance, the combination of ICG with chitosan has been shown to effectively kill both Gram-positive and Gram-negative bacteria under NIR light irradiation (Ni et al., 2022). This composite material is particularly useful for treating deep-seated infections that are otherwise difficult to reach using conventional treatment methods (Zhao et al., 2023).

Similarly, zinc phthalocyanine combined with polyaniline has shown high photothermal conversion efficiency and has been successfully applied to the treatment of bacterial infections (Bayar et al., 2023). This combination of organic dyes with polymer matrices ensures greater targeting of infected areas and reduces potential damage to surrounding healthy tissues (Zhou et al., 2022).

Polymer-based photothermal agents offer significant advantages in antimicrobial therapy, particularly for biofilm-associated infections and multidrug-resistant bacteria. By combining polymers with nanomaterials like metallic nanoparticles, carbon-based materials, and organic dyes, these agents deliver targeted photothermal effects with improved biocompatibility and stability.

However, several challenges remain in translating polymer-based photothermal agents into clinical use. These challenges include limited light penetration, high production costs, and concerns about long-term safety. Further optimization of polymer-nanoparticle combinations and the development of more efficient, low-cost, and biodegradable polymer-based photothermal agents will be critical for expanding their clinical applications.

Future research should also focus on creating multifunctional composite materials that combine PDT with other antimicrobial mechanisms, such as drug delivery or immune modulation. By integrating intelligent delivery systems, researchers develop polymer-based photothermal agents that offer more precise and controllable treatment options, advancing their role in antimicrobial therapy.