Jul 2026· Chemical Society Reviews· Vol 55, pp. 8653-8700· 2 citations· 220 references
Medicine
TL;DR
This review systematically surveys multimodal platforms that integrate PDT/PTT with chemodynamic therapy (CDT), sonodynamic therapy (SDT), gas therapy, antibiotics, and immunotherapy and highlights the rational design of nanomaterials that enable both reactive oxygen species (ROS) generation and photothermal conversion, thereby overcoming monotherapy limitations.
Abstract
Antimicrobial resistance (AMR) and bacterial biofilms pose a dire global health threat. To combat localized infections (e.g., chronic wounds, implant-associated infections), multimodal strategies combining photodynamic therapy (PDT) and photothermal therapy (PTT)-collectively referred to as photoactivated therapies (PT)-have emerged as promising antibiotic-sparing photoactivated approaches. This review systematically surveys multimodal platforms that integrate PDT/PTT with chemodynamic therapy (CDT), sonodynamic therapy (SDT), gas therapy, antibiotics, and immunotherapy. We highlight the rational design of nanomaterials that enable both reactive oxygen species (ROS) generation and photothermal conversion, thereby overcoming monotherapy limitations such as poor tissue penetration, hypoxia, and low efficiency. The applications of these systems in treating chronic wounds, implant infections, and deep-seated infections are discussed, with emphasis on material innovations including aggregation-induced emission (AIE) agents, metal-organic frameworks (MOFs), and biomimetic platforms. Finally, we critically evaluate challenges in targeting precision, long-term biosafety, and clinical translation, while outlining future directions toward smart responsive systems and AI-assisted design.
Bacterial infections, particularly those caused by multidrug-resistant pathogens and biofilm formation, have significantly undermined the efficacy of conventional antibiotics, highlighting the urgent need for novel antibacterial strategies. NIR-driven photothermal (PTT) and photodynamic therapies (PDT) have emerged as promising non-antibiotic approaches due to their noninvasive nature and precise spatiotemporal controllability. However, single-modality NIR treatments remain constrained by potential thermal damage to healthy tissues and reduced efficacy within the infection microenvironment. To address these limitations, researchers have developed NIR-mediated multimodal strategies that integrate complementary mechanisms for synergistic antimicrobial effects. Despite increasing studies, a systematic overview of NIR-based synergistic antibacterial strategies remains lacking. This review provides the first comprehensive focus on the combined application of NIR-mediated PTT/PDT with gas therapy (GT), chemodynamic therapy (CDT), immunotherapy, antibiotic adjuvants, and sonodynamic therapy (SDT). We summarize recent advances, discuss how these approaches overcome resistance, disrupt biofilm barriers, enhance antibacterial efficiency, and promote wound healing, and highlight the current challenges and prospects for clinical translation in this rapidly evolving field.
Mei Fang, Shu Gao, Jun Wang et al.· Small· 0 citations
Background: Antimicrobial resistance represents a growing global health challenge, necessitating the development of effective non-antibiotic antimicrobial approaches. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising localized antimicrobial strategy owing to its broad-spectrum activity, biofilm-targeting capability, and low propensity to induce resistance. However, its clinical translation remains restricted by limited photosensitizer (PS) performance, insufficient light penetration, oxygen dependency, biofilm-associated barriers, and the lack of standardized treatment protocols. Methods: This narrative review summarizes recent strategies developed to enhance the efficacy and translational potential of aPDT, including PS engineering, nanomaterial- and non-nanomaterial-based delivery systems, advanced light-source technologies, hypoxia-modulating approaches, and synergistic therapeutic strategies. In addition, current challenges associated with regulatory approval, manufacturing scalability, treatment standardization, and clinical implementation are discussed. Results: Recent advances have transformed aPDT from a conventional PS–light–oxygen system into a multifunctional antimicrobial platform. Emerging approaches improve bacterial targeting, biofilm penetration, reactive oxygen species generation, oxygen utilization, and therapeutic precision. Nevertheless, many advanced systems remain at the preclinical stage due to complexity, cost, safety concerns, and insufficient clinical validation. Conclusions: aPDT should be considered a targeted therapeutic option for accessible, localized, and biofilm-associated infections rather than a replacement for systemic antimicrobial therapy. Future clinical translation will depend on balancing technological innovation with biosafety, scalability, and protocol standardization. Strategies integrating intelligent PS design, oxygen regulation, and clinically feasible synergistic approaches may provide promising pathways toward the broader application of aPDT in antimicrobial management.
Antibiotic resistance is overburdening the health crisis around the globe. Misuse or overuse of antibiotics is one of the reasons for this issue. Therefore, it urges an alternative treatment strategy that can overcome the issue of bacteria being resistant. Photothermal and photodynamic therapies are emerging strategies, being an antibiotic-free solution to treat infections. This method utilizes antimicrobial treatment with heat and ROS, which makes it challenging for bacteria to become resistant. Earlier photothermal therapies required high-power laser sources, which had a significant risk of damaging healthy tissues in the vicinity. Recent research has shown that low-power NIR sources have great potential to achieve equivalent photothermal conversion efficiency when used with different sets of engineered photothermal agents and are also safe for use. A synergistic, low-power antimicrobial strategy combining the photodynamic properties and photothermal properties of the materials results in better efficiency. Additionally, leveraging the NIR-II range allows for deeper penetration into tissues, making it effective to treat deep-seated infections. This review highlights recent advancements in low-power NIR mediated PTT/PDT for mitigating drug-resistant bacteria, focusing on mechanisms, therapeutic outcomes, challenges, and future prospects.
T. Panda, Irfhan Sheriff, Jyoti Patel G et al.· Frontiers in Microbiology· 0 citations
Oral mucosal lesions (OMLs) comprise a diverse group of diseases affecting the oral mucosal tissues. Traditional treatments such as medication, surgery, laser therapy, and cryotherapy often produce significant side effects, including high recurrence rates due to drug resistance-associated recurrence and considerable tissue trauma, leading to unsatisfactory clinical outcomes. Photodynamic therapy (PDT), which uses photosensitizers, light at specific wavelengths, and oxygen to generate cytotoxic effects that induce cell apoptosis and necrosis, cause immunogenic cell death and microcirculation damage, and trigger local immune responses, has emerged as a promising minimally invasive alternative. PDT offers advantages including strong selectivity, minimal invasiveness, high targeting capability, and repeatable administration. However, clinical translation remains constrained by pharmacological barriers including restricted tissue penetration depth of therapeutic light, absence of standardized treatment protocols, and insufficient long-term efficacy data. This comprehensive review systematically examines the evolutionary development of photosensitizer generations, explores synergistic combination strategies integrating PDT with complementary therapeutic modalities, and critically evaluates current clinical applications across common OMLs types. By synthesizing current evidence and identifying knowledge gaps regarding drug-target interactions, this review aims to provide a robust foundation for advancing therapeutic agent development and guiding future research directions in PDT-based management of OMLs.
Guang-Miao Hu, Lin Wang, Lin Fan et al.· Frontiers in Pharmacology· 0 citations
Keratitis is a critical inflammation of the cornea caused by chemical agents due to bacterial, fungal, or viral pathogens. It significantly contributes to the global burden of vision loss and blindness in older adults. Antimicrobial treatment helps fight different types of bacteria. Conventional treatments are less effective owing to poor ocular drug bioavailability, rapid tear clearance, and drug-resistant microbes. Recent developments in nanotechnology hold promise for circumventing these limitations via improved delivery, targeting, and combination therapies. This study provides a critical review of the pathogenesis of microbial keratitis and a systematic assessment of emerging therapeutic approaches based on nanotechnology, including piezodynamic therapy (PZDT), photothermal therapy (PTT), photodynamic therapy (PDT), nanoenzymes, and metal ions. The assessment of each modality is based on its mechanism of action, effectiveness against biofilm-embedded pathogens, ability to modulate immune responses, and potential use with advanced drug delivery systems, such as microneedle patches, functionalized nanoparticles, and responsive hydrogels. This review also highlights the role of nanocarriers in improving drug retention, reducing systemic toxicity, and enabling targeted drug delivery to infected corneal tissue. Toxicity, regulatory hurdles, and therapeutic consistency pose challenges to clinical translation. This review presents a comprehensive outlook on the potential of nanomedicine in keratitis therapy using microbiology, immunology, materials science, and clinical ophthalmology. The goal is to inform future research and foster interdisciplinary approaches that will result in treatments that are more effective, safer, and patient-focused for this vision-impairing condition. Nanotechnology-enabled ocular therapies may overcome existing drug delivery limitations and improve clinical outcomes in microbial keratitis, as noted in this review.
Ruchi Tiwari, D. G, Vasanth Kumar Mohan et al.· Recent Advances in Anti-Infe...· 1 citation
This review highlights mechanisms, recent advances, and translational challenges of natural PS‐based nanotherapeutics across multiple cancers, emphasizing strategies to improve delivery, selectivity, and therapeutic outcomes for next‐generation PDT.
