Enamel demineralization, characterized by the formation of white spot lesions, is a common complication in clinical orthodontic treatment [1]. If left unaddressed, this condition can progress to dental caries, structural damage to teeth, and in severe cases, significant defects in dental tissue [2]. In a cross‑sectional study by Ogaard et al., the median white‑spot lesion score in orthodontically treated patients was significantly higher than in an untreated control group. Notably, lesions persisting more than five years after treatment completion continued to compromise dental esthetics [3]. The alteration of the oral microenvironment during orthodontic treatment contributes to an increased risk of plaque accumulation. This is primarily due to the difficulty in thoroughly cleaning around orthodontic appliances and residual food particles [4]. Plaque accumulation on orthodontic brackets and tooth surfaces leads to elevated levels of Streptococcus mutans and a reduction in salivary pH. These changes create an acidic environment conducive to enamel demineralization, ultimately resulting in the formation of white spot lesions (WSLs) [5]. Despite the recognition of this issue, there is currently no universally accepted standard for preventing orthodontic leukoplakia. Preventing plaque accumulation around orthodontic appliances remains central to managing this condition.

Fluoride and casein phosphopeptide–amorphous calcium phosphate (CPP‑ACP) are currently the most widely used agents for the prevention and treatment of orthodontic white‑spot lesions (WSLs) [6,7]. Fluoride exerts its anticariogenic effect largely by inhibiting bacterial glycolytic enzymes (e.g. enolase), thus reducing acid production and overall plaque activity [8,9]. CPP‑ACP, on the other hand, stabilizes high local concentrations of calcium and phosphate ions at the tooth surface and interferes with the adhesion of cariogenic bacteria to the acquired pellicle, thereby limiting bacterial aggregation and lesion initiation [7]. Nevertheless, neither fluoride nor CPP‑ACP is capable of completely preventing the formation of plaque biofilms around orthodontic appliances, and WSLs still develop in a substantial proportion of patients despite their use [10]. Given the close pathophysiological parallels between orthodontic WSLs and conventional dental caries—where plaque accumulation and acidogenic bacterial biofilms are the primary etiological drivers—there is a clear need to explore more potent anti‑biofilm strategies for effective prevention and long‑term management [8,11].

In recent years, photodynamic therapy (PDT) has gained attention as a promising approach to inhibit plaque growth and reduce local inflammation [12]. PDT involves the activation of a photosensitizer by an external light source, leading to the generation of singlet oxygen or other reactive oxygen species (ROS) from surrounding oxygen molecules [13]. These ROS exert antimicrobial effects and modulate biological processes [14]. PDT offers advantages such as ease of operation, broad-spectrum efficacy, and high efficiency [15]. In the treatment of oral infectious diseases, light-activated antibacterial photosensitizers have demonstrated efficient bacterial inactivation [16,17]. Near-infrared (NIR) responsive nanocarriers have shown considerable promise in clinical applications [18]. The NIR region (700–1100 nm), often referred to as the "therapeutic window" for biological tissues, allows for strong tissue penetration [19]. For example, a commonly used 980 nm semiconductor NIR laser can penetrate tissues to depths of 3–5 cm, enabling irradiation of lesion areas without dead zones. To avoid damage to normal tissues due to untargeted local heating, researchers have developed positive temperature coefficient (PTC) nanoformulations that rely on photothermal conversion, thereby addressing potential risks associated with PDT [20,21]. Polydopamine (PDA) is a promising material in this context due to its strong NIR absorption, high photothermal conversion efficiency, excellent biocompatibility, and biodegradability, without causing long-term toxicity [22,23]. These properties make PDA an ideal candidate for coating nanoparticles that combine photodynamic and photothermal therapies [[24], [25], [26]]. The excellent adhesion properties of PDA allow it to form a shell around polymer nanocarriers and inorganic nanoparticles [27,28]. Additionally, pegylation of PDA can modify its surface properties to reduce interactions with the immune system, providing an "immune stealth" effect [29].

Ag⁺/Cu²⁺ bimetallic nanoparticles (BNPs) exert their antibacterial effects through multiple interconnected mechanisms [30,31]:

Membrane Adhesion and Disruption: The BNPs adhere to bacterial cell membranes, inducing structural alterations that compromise membrane integrity. This increases permeability and disrupts critical cellular functions, including ATP synthesis and transport [30,32].

Intracellular Penetration and Damage: Upon internalization into the cytoplasm and nucleus, the particles disrupt mitochondrial function, destabilize and denature proteins, and interfere with DNA interactions [33].

Reactive Oxygen Species (ROS) Generation: The BNPs induce cytotoxicity by catalytically generating ROS, which oxidatively damage essential bacterial components including proteins, lipids, and DNA bases [34,35].

Signal Transduction Interference: They modulate cellular signaling pathways by altering phosphotyrosine profiles.

Synergistic Enhancement and Reduced Cytotoxicity:

The Ag⁺/Cu²⁺ BNPs exhibit synergistic antibacterial efficacy while simultaneously demonstrating reduced cytotoxicity compared to their monometallic counterparts [31,36,37]. This beneficial profile is primarily attributed to the incorporation of Ag⁺, which significantly suppresses the oxidative propensity of Cu²⁺. The formation of Ag-CuONPs creates a more stable structure that limits oxygen ingress. This enhanced stability, combined with the bimetallic synergy, enables a controlled, sustained release of ions – a key factor in both efficacy and biocompatibility [[38], [39], [40], [41], [42]].

Controlled Release via PLGA/PDA Encapsulation:

To further optimize performance, the BNPs are encapsulated within a poly(lactic-co-glycolic acid) (PLGA) shell, uniformly coated with a polydopamine (PDA) layer. This core-shell structure significantly mitigates the initial burst release of metal ions, thereby substantially reducing acute cytotoxicity and ensuring sustained, synergistic release of Ag⁺ and Cu²⁺ [[43], [44], [45]].

Near-Infrared (NIR) Light-Triggered Activation:

Crucially, the PDA coating confers photothermal responsiveness. Under NIR laser irradiation, PDA rapidly converts light to heat, inducing the PLGA shell to reach its glass transition temperature (Tg). This thermally triggered phase transition enables the on-demand release of therapeutic doses of Ag⁺/Cu²⁺ BNPs. This spatiotemporal control allows the nanoplatform to achieve potent antibacterial effects while maintaining low systemic cytotoxicity [46,47].

In this study, we constructed Ag/CuO nanoparticles encapsulated within PLGA nanospheres and further coated them with PDA to develop laser-mediated, thermally responsive, slow-release Ag/CuO nanomaterials. Under NIR light excitation, this platform exhibited antibacterial activity against Streptococcus mutans. Specifically, high-efficiency energy transfer and the slow and controlled release of Ag/CuO nanoparticles were achieved under excitation with a 980 nm semiconductor NIR laser, resulting in photodynamic antibacterial and bacteriostatic effects. This innovative method offers a new clinical strategy for the prevention and management of orthodontic white‑spot lesions.