Fluorescent nanomaterials smaller than 10 nm can disrupt drug-resistant bacteria through multiple mechanisms while enabling real-time imaging, offering a new direction in antimicrobial strategy development.
(Nanowerk Spotlight) Hospital wards, neonatal units, and intensive care facilities across the world are seeing a growing number of infections that no longer respond to antibiotics. Bacteria once easily managed with routine treatments are now evolving faster than our drugs can keep up. According to estimates published in The Lancet and cited by the World Health Organization, antimicrobial resistance (AMR) was directly responsible for 1.27 million deaths in 2019 and contributed to nearly 5 million deaths worldwide that year. A follow-up analysis published in 2024 revised these figures upward, estimating that in 2021, around 4.71 million deaths were associated with bacterial AMR, including 1.14 million directly attributable deaths.
Projections from the Global Research on Antimicrobial Resistance (GRAM) project warn that by 2050, annual death rates could reach up to 8.2 million, with total AMR-related deaths between 2025 and 2050 exceeding 169 million.
The growing inefficacy of antibiotics is not just due to overuse in clinics and agriculture—it also reflects a deeper biological challenge. Bacteria form biofilms: dense, structured communities that coat surfaces, shield cells from attack, and limit the diffusion of drugs. These biofilms are common on medical implants, wounds, and tissues, and their physical architecture protects bacteria from even the most potent antibiotics. Inside these biofilms, bacteria are harder to reach, harder to kill, and more likely to develop resistance.
With no quick pharmaceutical fix in sight, researchers are rethinking the problem. What if, instead of relying solely on chemicals to block bacterial enzymes or cell division, we could design materials that physically interact with bacteria, disrupt them at multiple points, and—crucially—track those interactions in real time?
These materials, which include carbon dots, quantum dots, and metal nanoclusters, are small enough to enter bacteria, bright enough to be visualized under fluorescence microscopy, and reactive enough to disrupt microbial structures.
The review situates these materials not as speculative technologies, but as real, experimentally verified systems with demonstrated performance in bacterial control. It details how they are made, how they interact with pathogens, and what still needs to be understood before they can be translated into clinical or industrial use.
Schematic diagram of 0D FNMs: preparation, properties, and their antibacterial applications. (Image: Reprinted from DOI:10.1002/anbr.202500110, CC BY) (click on image to enlarge)
Preparation methods are divided into two main categories: top-down and bottom-up.
Top-down approaches begin with larger materials and reduce them to nanoscale dimensions through physical force. Techniques include ball milling, ultrasonic grinding, and laser ablation. These methods are often low-cost and scalable but can yield particles with inconsistent properties.
Bottom-up approaches use chemical reactions to build nanomaterials from atoms or molecules. These include hydrothermal, solvothermal, microwave-assisted, and template-based methods. Bottom-up synthesis allows more precise control over particle size, composition, and functionality.
One key advantage of bottom-up methods is their compatibility with biomass-derived precursors, such as fruit extracts or plant leaves. These materials are renewable and cost-effective, and often introduce beneficial elements like nitrogen, sulfur, or phosphorus into the final product.
For instance, using citric acid and o-phenylenediamine under microwave irradiation, researchers have synthesized carbon dots (CDs) in under four minutes. The resulting particles exhibit strong blue fluorescence, high quantum yield (a measure of light-emission efficiency), and excellent biocompatibility—all without requiring extreme temperatures or pressures.
Other promising materials include metal nanoclusters (MNCs) synthesized using biomolecules as templates. DNA, proteins, and peptides not only provide structural scaffolding but can also serve as reducing agents and stabilizers. These template-based methods offer atomic-level control over particle formation and avoid toxic reagents or solvents. By designing specific DNA sequences or protein structures, researchers can fine-tune the optical and antibacterial properties of the resulting nanoclusters.
The review highlights several mechanisms by which 0D fluorescent nanomaterials act against bacteria:
Reactive oxygen species (ROS) generation: Many FNMs promote the formation of molecules like hydrogen peroxide or hydroxyl radicals that damage bacterial membranes, proteins, and DNA.
Membrane disruption: Due to their small size and often positive surface charge, these nanomaterials bind to bacterial cell membranes and destabilize their structure.
Intracellular interference: Once inside the cell, some materials disrupt genetic processes or enzyme function, weakening or killing the bacterium.
Metal ion release: In the case of metal-based nanoclusters, the release of ions like Ag⁺ enhances toxicity to bacteria while remaining relatively safe for human cells.
Combined effects: These mechanisms often operate in tandem. For instance, silver nanoclusters can release ions that generate ROS, producing a compounding antibacterial effect.
Notably, several materials are designed to respond to specific environments, such as the acidic pH found in bacterial biofilms. One example is a pH-responsive silver nanocluster that remains inactive under normal conditions but disassembles in acidic environments, releasing toxic ions only at infection sites. This targeted approach reduces off-target effects and improves safety for surrounding healthy tissues.
The review also summarizes experimental results for various materials and pathogens. For instance, multifunctional carbon dots achieved over 96% inhibition of E. coli at 14 μg/mL. Silver nanoclusters showed minimum inhibitory concentrations (MICs) as low as 9 μg/mL against Staphylococcus aureus. Such results are promising not only for medical settings but also for applications in agriculture, food safety, and water purification.
Some of the materials also exhibit dual functionality—they can be used to both image and kill bacteria, allowing researchers to track the movement and localization of the materials inside tissues or biofilms. This built-in fluorescence is an intrinsic property of the materials, enabling real-time, non-invasive monitoring of antibacterial action without additional dyes or markers.
Despite their promise, the paper acknowledges several remaining challenges. These include batch-to-batch reproducibility, toxicity at higher doses, and limited understanding of long-term effects in biological systems. While many materials have shown low toxicity in cell cultures, full safety evaluations in animal models and humans are still needed. In addition, large-scale, standardized manufacturing methods must be developed for any of these systems to move beyond the lab.
Still, the work represents a shift in how antimicrobial technologies can be conceived. Instead of relying solely on molecular inhibition, these materials attack pathogens through multi-pronged physical and chemical mechanisms, reducing the risk of resistance development. Their small size, controllable properties, and inherent luminescence make them promising candidates for next-generation infection control strategies, particularly in scenarios where traditional antibiotics are no longer effective.
In a world facing the increasing burden of drug-resistant infections, zero-dimensional fluorescent nanomaterials offer a new class of antimicrobial tools—measurable, tunable, and potentially transformative in both function and form.
For authors and communications departmentsclick to open
Lay summary
Prefilled posts
Nanowerk Newsletter
Get our Nanotechnology Spotlight updates to your inbox!
Thank you!
You have successfully joined our subscriber list.
Become a Spotlight guest author! Join our large and growing group of guest contributors. Have you just published a scientific paper or have other exciting developments to share with the nanotechnology community? Here is how to publish on nanowerk.com.
