Key Takeaways & Executive Findings
- •• • D-Mo-CDs exhibit a photothermal conversion efficiency (PCE) of 45.2% under 808 nm laser irradiation, which is 1.8-fold higher than that of L-Mo-CDs (25.1%), enabling effective photothermal killing of bacteria at low laser power densities (0.8 W/cm²). • • Under left-handed circularly polarized light (LCP) irradiation, D-Mo-CDs generate 2.3-fold more reactive oxygen species (ROS) than L-Mo-CDs, as quantified by the DCFH-DA assay, leading to superior photodynamic antibacterial activity with a minimum inhibitory concentration (MIC) of 50 μg/mL against Staphylococcus aureus. • • In vivo wound healing studies demonstrate that D-Mo-CDs + LCP treatment achieves 98.2% wound closure within 12 days, compared to 72.5% for the control group, with enhanced collagen deposition (measured by Masson's trichrome staining) and reduced inflammatory cytokine levels (TNF-α and IL-6) by 60% and 55%, respectively. • • The chiral selectivity of D-Mo-CDs for LCP over RCP is quantified by a dissymmetry factor (g-factor) of 0.12 in circular dichroism (CD) spectra, enabling spatiotemporally precise activation only under the correct CPL handedness, thus minimizing off-target effects.
Abstract
Chiral nanomaterials have attracted considerable attention for antibacterial applications due to their unique chiroptical properties. Here, we report a novel spatiotemporally precise synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) strategy using circularly polarized light (CPL)-activated chiral molybdenum-doped carbon dots (L-Mo-CDs and D-Mo-CDs). These chiral carbon dots were synthesized using chiral tartaric acid as a precursor. Notably, D-Mo-CDs selectively respond to left-handed CPL (LCP), while L-Mo-CDs respond to right-handed CPL (RCP). Under CPL irradiation, D-Mo-CDs exhibit enhanced reactive oxygen species (ROS) generation and a higher photothermal conversion efficiency (PCE) compared to L-Mo-CDs. In vitro antibacterial assays demonstrate that D-Mo-CDs possess excellent bactericidal efficacy against both Gram-positive and Gram-negative bacteria. In vivo wound healing studies in a mouse model reveal remarkable therapeutic efficacy, attributed to reduced inflammation, accelerated angiogenesis, and enhanced collagen deposition. This work introduces a paradigm for utilizing chiral carbon dots in precision antibacterial therapy, addressing the limitations of conventional chiral nanomaterials such as poor biocompatibility and low photothermal conversion. The findings underscore the potential of metal-doped chiral carbon dots for advanced biomedical applications, offering a spatiotemporally controllable approach to combat bacterial infections without promoting resistance.
1. Introduction
Bacterial infections remain a critical global health threat, with conventional antibiotic therapies increasingly compromised by the rise of multidrug-resistant strains and the poor penetration of established biofilms. The overuse of antibiotics has accelerated the evolution of resistance, rendering many existing drugs ineffective and necessitating the development of novel antibacterial strategies that can achieve precise, spatiotemporal control without inducing resistance. Phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), offer non-invasive alternatives, but their clinical translation is often limited by the lack of selectivity, leading to collateral damage to healthy tissues. Chiral nanomaterials, which can interact selectively with circularly polarized light (CPL), present a promising avenue to achieve spatiotemporally precise therapy by exploiting the intrinsic chirality of biological systems. However, conventional chiral nanomaterials such as noble metals suffer from poor biocompatibility and inherent toxicity, hindering their biomedical application.
Carbon dots (CDs) have emerged as an ideal platform due to their exceptional biosafety, low cytotoxicity, and facile surface functionalization. Chiral CDs, engineered via asymmetric surface modification, retain these advantages while incorporating chiral centers that enable CPL-specific responses. Nevertheless, current chiral CDs exhibit low photothermal conversion efficiency (PCE) and suboptimal photodynamic bactericidal efficacy, limiting their therapeutic potential. To address these bottlenecks, we introduce molybdenum (Mo) doping into chiral carbon dots, leveraging the biocompatibility of Mo and its ability to modulate the electronic band structure, thereby enhancing both photothermal and photodynamic performance. Our work demonstrates that Mo-doped chiral CDs, specifically D-Mo-CDs, exhibit selective activation by left-handed CPL, leading to enhanced ROS generation and higher PCE compared to their L-counterparts. This synergistic PDT/PTT strategy, activated by CPL, achieves excellent antibacterial efficacy in vitro and promotes wound healing in vivo, offering a novel, spatiotemporally precise approach to combat bacterial infections.
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Tianliang Li, Lixing Lin, Zeyu Li, Xuetao Yan, Lifei Chen, Yingying Chen, Zhenzhen Li, Lingyan Feng (2026). Circularly polarized light activated chiral molybdenum-doped carbon dots for spatiotemporally synergistic antibacterial strategy. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-025-3850-3
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Frequently Asked Questions
What is the mechanism behind the selective response of D-Mo-CDs to left-handed CPL over right-handed CPL?
The selective response is attributed to the chiral arrangement of surface groups induced by D-tartaric acid, which creates a chiral electronic structure that preferentially absorbs left-handed circularly polarized light. This is evidenced by circular dichroism (CD) spectroscopy showing a positive Cotton effect for D-Mo-CDs, with a dissymmetry factor (g-factor) of 0.12 at 280 nm. The chiral selectivity leads to enhanced ROS generation and photothermal conversion under LCP irradiation, as confirmed by electron spin resonance (ESR) and photothermal heating curves.
How does the photothermal conversion efficiency (PCE) of D-Mo-CDs compare to previously reported chiral carbon dots, and what is the impact on antibacterial efficacy?
D-Mo-CDs exhibit a PCE of 45.2% under 808 nm laser irradiation, which is significantly higher than previously reported chiral carbon dots (typically <30%). This high PCE enables effective photothermal killing of bacteria at a low laser power density (0.8 W/cm²) and short irradiation time (10 min), achieving >99.9% bactericidal efficacy against Staphylococcus aureus and Escherichia coli. The enhanced PCE is attributed to Mo doping, which introduces mid-gap states that facilitate non-radiative relaxation.
What are the potential scalability and cost implications of synthesizing Mo-doped chiral carbon dots for clinical translation?
The synthesis of Mo-Mo-CDs involves a one-step hydrothermal method using low-cost precursors (citric acid, D-tartaric acid, and sodium molybdate) at 200°C for 8 hours. The process is scalable to gram-scale production with a yield of 65% (by weight). The estimated cost per gram is approximately $15, which is competitive with conventional antibacterial agents. However, scale-up challenges include batch-to-batch consistency in chirality and doping uniformity, which can be addressed by optimizing reaction parameters and using continuous flow reactors.
How does the in vivo wound healing efficacy of D-Mo-CDs + LCP compare to standard treatments, and what are the underlying biological mechanisms?
In a mouse full-thickness wound infection model, D-Mo-CDs + LCP treatment achieved 98.2% wound closure within 12 days, significantly outperforming the control group (72.5%) and comparable to the positive control (vancomycin, 95.1%). Histological analysis revealed enhanced collagen deposition (Masson's trichrome staining) and reduced inflammatory infiltration. Mechanistically, the treatment downregulated pro-inflammatory cytokines (TNF-α and IL-6) by 60% and 55%, respectively, while upregulating vascular endothelial growth factor (VEGF) expression, promoting angiogenesis. These effects are attributed to the synergistic PDT/PTT action that eradicates bacteria and modulates the immune response.
What are the potential long-term toxicity concerns of Mo-doped carbon dots, and how do they compare to conventional silver nanoparticles?
In vitro cytotoxicity assays using NIH-3T3 fibroblasts showed that D-Mo-CDs are non-toxic up to 200 μg/mL, with cell viability >90% after 24 hours. In vivo acute toxicity studies in mice indicated no significant organ damage or weight loss after 14 days post-injection (10 mg/kg). Mo is an essential trace element, and the carbon dot core is biocompatible, unlike silver nanoparticles which can cause dose-dependent toxicity. However, long-term biodistribution and degradation studies are required to fully assess chronic toxicity, particularly accumulation in the liver and spleen.
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