The challenges posed by antibiotic abuse and biofilm associated barriers have emerged as critical issues in modern medicine [1], [2]. Microbial cells form bacterial biofilms through the secretion of extracellular polymeric substances (EPS) and intercellular adhesion. The resistance of biofilms against external factors is controlled by the quorum sensing (QS) system, a bacterial communication network that coordinates collective behaviors via chemical signaling molecules. This mechanism enhances antibiotic tolerance, biofilm resistance, expression of antibiotic resistance genes, and the acquisition of resistance determinants [3], [4]. Studies have demonstrated that quorum sensing inhibitors (QSI) can effectively suppress bacterial growth and disrupt biofilms [5], [6], [7], [8]. For example, curcumin (Cur), a natural compound isolated from Curcuma longa, has been confirmed in recent studies to effectively inhibit both biofilm formation and bacterial growth by inhibiting QS systems [9], [10]. However, the application of Cur faces challenges due to inherent cytotoxicity—nonspecific delivery may cause damage to healthy tissues [11], [12]. Consequently, the precise control release of Cur has emerged challenge requiring urgent resolution.
In the field of nano-antibacterial technology, silver ions (Ag⁺) have been widely recognized as effective broad-spectrum antimicrobial agents. Studies revealed that Ag⁺ exerts antibacterial activity through multiple mechanisms, including disruption of cell membrane integrity, induction of reactive oxygen species (ROS) generation, interference with protein function via chelation and DNA damage [13], [14]. However, the application of silver nanoparticles (AgNPs) confronts a critical bottleneck-the biotoxicity. The primary challenge stems from the uncontrolled release of Ag+ under physiological conditions, which can trigger highly toxic reactive oxygen species to cause direct damage to healthy tissues [15], [16], [17]. The controlled release of Ag⁺ from AgNPs in the bacterial inflammatory microenvironment can significantly reduce the potential cytotoxicity of free Ag⁺ [18], [19]. Thus, there is an urgent need to engineer a smart nanoplatform with multifunctional synergistic properties for on-demand release to address antibiotic abuse and biofilm associated infections.
The temperature-sensitive phase change materials (PCM) have attracted significant attention for smart drug delivery owing to their unique physicochemical properties [20], [21], [22]. Among these, 1-tetradecanol-based PCM exhibit excellent biocompatibility, low toxicity, sustained release capability and gated release behavior [23], [24]. The characteristics of reversible solid-liquid phase transition within a narrow temperature window (38–39°C) make 1-tetradecanol an ideal candidates for controlling drug release [25]. Inspired by that, we hypothesized that precise temperature control of the local bacterial inflammatory microenvironment during photothermal therapy (PTT) could trigger PCM phase transition. The resultant temperature increase would induce material transition, enabling spatiotemporally controlled release of both QSI and AgNPs at the infection site [26], [27]. Moreover, PTT offers distinct advantages as a non-chemotherapeutic intervention, including remote controllability, site specificity and minimal invasiveness [28], [29], [30]. Under NIR, localized heating can be achieved to effectively kill bacteria. Among various PTT nanoagents reported to date, mussel-inspired polydopamine (PDA) has been widely investigated due to excellent biocompatibility and photothermal conversion ability [31]. This suggests that photothermal intervention (PTI) modulation of PCM properties could ensure on-demand release of both QSI and AgNPs. Thus, developing a new generation of temperature-dependent, on-demand release nano-antibacterial platforms using thermosensitive materials holds great promise for enhancing antibacterial and antibiofilm performance.
In this study, we developed a temperature-sensitive, on-demand release multifunctional nano-antibacterial system (PDA@Ag@Cur@PCM) that achieves precise drug release through NIR-triggered, thereby synergistically enhancing antibacterial and antibiofilm performance. Specifically, AgNPs were anchored on PDA surfaces via in situ reduction, while Cur was encapsulated through π-π stacking interactions. An outer 1-tetradecanol coating ensured controlled payload retention until NIR-triggered phase transition, enabling stimulus-responsive drug release. The nanosystem collaborates with Ag+ mediated membrane destruction, Cur-driven QSI and local PTT to enhance antibacterial and antibiofilm performance. Experimental results demonstrated significant antibacterial activity against both E. coli and S. aureus, with the ATP level and total carbohydrate content in the PACP+NIR treated group being significantly lower than the other control groups. Cytocompatibility assessment confirmed > 95 % viability in HUVEC cells, highlighting antibacterial potential. The multimodal platform represents an advanced antibacterial strategy that integrates NIR-triggered, temperature-sensitive, rapid phase transition and on-demand release to enhance antibacterial and antibiofilm performance.
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