Open research questions in Carbon and Quantum Dots Applications

What the literature leaves open

• absorption intrinsic tune and in toxicity, vivo behaviour, Although CQDs demonstrate considerable potential, their long-term complex interactions within biological systems remain incompletely understood, presenting challenges regarding safe and effective clinical translation.

  Carbon Quantum Dots as Versatile Nanosystems for Biomedical Innovation: Mechanisms, Applications, and Translational Prospects · 2026 · DOI

• Jasdev Singh Maan 1, Milind Kuruvath Santhosh 1, Stevelyn Jia Xin Lee 1, Nicole Zi Yu Leow 1, Anis Sofia binti Mohd Adli 1, Charlotte Jia Qi Tai 1, Jia Hui Lim 1, Yasheni Muniandy 1, Chun-Wai Mai 2, Tong Ling Tan 3, Soi Moi Chye 4, Rhun Yian Koh 4 and Chooi Ling Lim 4* 1School of Health Sciences, IMU University, Kuala Lumpur, Malaysia, 2Institute of Research, Development and Innovation, IMU University, Kuala Lumpur, Malaysia, 3Department of Pharmaceutical Chemistry, School of Pharmacy, IMU University, Kuala Lumpur, Malaysia, 4Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur, Malaysia Carbon quantum dots (CQDs) represent a rapidly developing class of fluorescent nanomaterials with increasing relevance in biomedical research and application. Their tuneable photoluminescence (PL), favourable biocompatibility, and versatile surface chemistry has supported applications in bioimaging, biosensing, and therapeutic strategies. Advances in top-down, bottom-up, and green synthesis routes have improved control over emission profiles, heteroatom doping, and surface functionalisation. Recent work has begun to elucidate how synthesis conditions and surface states govern biological interactions, intracellular transport, and subcellular localisation. This review provides an updated, mechanistic evaluation of these developments, with particular emphasis on how defined structural attributes influence antimicrobial activity, organelle-specific targeting, and integrated imaging-therapy platforms. Despite these advances, significant challenges continue to hinder clinical translation. These include variability in synthesis protocols, inconsistent batch-to-batch reproducibility, and insufficient data on long-term toxicity and biodistribution. The absence of standardised characterisation frameworks and clear regulatory pathways further complicate translational progress. Through critically linking synthesis strategies to surface chemistry and biological behaviour, this review depicts key design considerations necessary for advancing CQDs toward clinical application in next- generation nanomedicine. Keywords: bioimaging, biosensing, carbon quantum dots, drug delivery, nanomaterials INTRODUCTION Nanostructured carbon allotropes, including fullerenes, carbon nanotubes (CNTs), and graphene, have in nanotechnology and bioengineering [1]. Carbon dots (CDs) represent a broad class of photoluminescent, nanoscale carbon-based nanomaterials, among these, carbon quantum transformed materials science while paving novel possibilities *Correspondence Chooi Ling Lim, [email protected] Received: 27 November 2025 Revised: 15 February 2026 Accepted: 25 February 2026 Published: 02 April 2026 Citation: Maan JS, Santhosh MK, Lee SJX, Leow NZY, Mohd Adli ASb, Tai CJQ, Lim JH, Muniandy Y, Mai C-W, Tan TL, Chye SM, Koh RY and Lim CL (2026)

  Carbon Quantum Dots as Versatile Nanosystems for Biomedical Innovation: Mechanisms, Applications, and Translational Prospects · 2026 · DOI

• Carbon dots have rapidly evolved from a laboratory curiosity into a widely explored class of carbon-based nanomaterials with growing relevance for biomedical, environmen- tal, and technological applications. Despite this progress, the present review highlights that the current understanding of carbon dot cytotoxicity and biosafety remains frag- mented and strongly context dependent. Apparent contradictions in reported toxicity outcomes do not reflect the intrinsic inconsistencies of the material itself, but rather arise from synthesis-dependent heterogeneity, methodological limitations, and insufficiently standardized evaluation strategies. A central conclusion of this review is that carbon dot toxicity cannot be meaningfully discussed in binary terms such as “toxic” or “non-toxic.” Instead, biological responses emerge from the interplay between physicochemical properties, synthesis history, exposure conditions, and experimental context. Factors such as surface chemistry, heteroatom doping, dose, illumination, and material transformation over time jointly define biological outcomes and must be considered in an integrated manner. Importantly, statistical analysis of the compiled dataset indicates that the apparent low toxicity of carbon dots reported in the literature may partly reflect the dominance of specific cellular models, particularly HeLa cells, which are frequently used in toxicity assays. When toxicity outcomes are analyzed across different biological models, substantial variability emerges, suggesting that the biological context plays a critical role in determining observed cytotoxic responses. Looking forward, several key challenges must be addressed to advance the field toward reliable safety assessment and responsible application. First, greater emphasis should be placed on synthesis reproducibility and batch-to-batch variability, with explicit reporting of material identity and inter-batch differences. Without such transparency, the accumulation of toxicity data risks reinforcing ambiguity rather than resolving it. Second, toxicity evaluation strategies should evolve from single-endpoint screening toward https://doi.org/10.3390/ijms27093782 Int. J. Mol. Sci. 2026, 27, 3782 37 of 43 multiparametric and context-aware frameworks that account for assay interference, non- linear dose responses, and photo-induced effects. Environmental fate and transformation represent another critical frontier. As car- bon dots increasingly enter consumer products and biomedical applications, understand- ing their long-term behavior under realistic environmental and biological conditions— including photodegradation and the formation of transformation products—will be essen- tial for comprehensive risk assessment. The frequent use of natural or biomass-derived precursors, while attractive from a sustainability perspective, should not be equated with inherent safety without rigorous evaluation of the resulting materials. Importantly, the growing

  Understanding the Toxicity of Carbon Dots: The Role of Synthesis Variability, Surface Chemistry, and Biological Context · 2026 · DOI

• Furthermore, regula- tory pathways remain unexplored: biomedical devices require ISO 10,993 compliance; food contact applications must meet EU 1935/2004 or FDA requirements; and CQDs as novel nanomaterials face REACH classification.

  Biomass based carbon quantum dots in sensor applications: a review (2021–2025) · 2026 · DOI

• Future research should focus on simplifying preparation routes, improving biocompatibility for in vivo applications, developing smartphone- integrated systems, and promoting the clinical and commercial transformation of MQD-based biosensing technologies.

  Recent Advances in the Applications of MXene Quantum-Dots for Biosensing · 2026 · DOI

• Although carbon dots have significant optoelectronic potential, a number of outstanding material issues need to be resolved before commercial translation can take place: 5.1 Low reproducibility of emission properties Because polymerization, carbonization, and passivation occur simultaneously during bottom-up synthesis, even small changes in batch temperatures or heating rates can drastically change surface topologies (Kwon et al., 2014; Rigodanza et al., 2021). To guarantee consistent optical performance from batch to batch, standardized, automated synthesis processes must be developed. Furthermore, in parallel tracking systems, integrating physics-based rendering with neural network embeddings is essential to maintain multi-source illumination color constancy despite these material variances (Xue et al., 2025). 5.2 Scale-up limitations High quantum efficiency production techniques, such microwave or hydrothermal synthesis, are usually limited to tiny batch sizes (He et al., 2020). Thermal and mass-transport gradients are frequently introduced when scaling up to commercial levels, which widens particle size distributions and deteriorates color purity. This optical variance presents similar challenges to low-light imaging frameworks, where multiconditional diffusion probabilistic models (such as MCLL- Diff) are deployed to dynamically adapt and enhance contrast under poor visibility conditions (Chen et al., 2025). 5.3 Stability under device operating conditions CDs are subjected to extended exposure to heat, moisture, and strong UV fluxes when incorporated into high-power LEDs or solar cells. In these circumstances, thermal desorption or photo-oxidation of the surface functional groups that passivate fault states may occur, resulting in irreversible luminescence degradation and device failure (Essner and Baker, 2017). To monitor macro-structural shifts and thermal anomalies linked to this degradation, highly precise diagnostic self-mixing such as using interferometry with intracavity frequency-doubling solid-state lasers to trace micro-vibration signatures (Feng et al., 2026). tools are required, To accelerate the practical deployment of these materials in complex optical systems, research must also bridge the gap between material synthesis and advanced system-level calibration. In next- generation optoelectronics and light-emitting systems, single-view neural illumination estimation frameworks are now utilized to dynamically edit and adjust complex environmental lighting conditions for high-fidelity light field displays (He et al., 2026). Concurrently, to safeguard long-term stability and catch defects early on a industrial scale, photovoltaic module inspection platforms are implementing advanced electromagnetic induction-assisted scanning photoluminescence et al.,2026). Bridging these materials-level improvements with systematic, automated imaging diagnostics will be key to unlocking the full potential of next-generation carbon dot optoelectronics. imaging (Hong served semiconductors have investigations have demonstrated Although carbon dots have recently emerged as versatile nanomaterials for optoelectronic applications, many of the fundamental concepts governing their optical performance have evolved from extensive studies on conventional semiconductor materials. Wide-bandgap as benchmark systems for understanding the relationship between crystal quality, defect density, and radiative recombination. synthesis

  Illuminating innovations: leveraging the optoelectronic capabilities of carbon dots for advanced displays, sensors, and renewable energy solutions · 2026 · DOI

• Nevertheless, several limitations and challenges in this study remain to be addressed. Third, the potential value of O-CDs in targeted imaging and theranostics could be further explored. For instance, the fluorescence-based quantitative results have not yet been validated by standard reference methods such as HPLC, and the multifunctional applications of the solid- state samples have not been systematically explored beyond preliminary bioimaging investigations.

  Synthesis of high quantum yield orange carbon dots as multifunctional fluorescence probe in VB12 detection and bio-imaging · 2026 · DOI

• CQDs have attracted significant interest in recent decades owing to their character- istics and possible use in various health and beauty-related disciplines. However, there is still an untapped potential for the development of CQDs. According to Alkhatib et al., activated charcoal can be utilized therapeutically and can absorb toxins and toxic com- pounds introduced into the stomach and intestine [92]. Charcoal Plus DS and CharcoCap are two popular names for dietary supplements used to absorb the gas produced by the stomach. Studies on CQDs as supplements or diarrhea remedies should be performed because of their hydrophilic nature and low toxicity. Due to their special qualities, such as biocompatibility, chemical stability, and adjustable PL, CQDs are currently exploited in pharmaceutical formulations and nanomedicine. Three gel formulations loaded with N- hydroxyphthalimide CQDs (NHF-CDs) were produced to assess their anticancer activities, according to Corina-lenuta et al. [95]. However, the impact of CQDs on peptide or protein fibrillation has not been thoroughly investigated. It has also been suggested that CQDs can prevent fibrillation of human insulin as a treatment method for disorders linked with peptide or protein fibrillation. Charcoal-based mouthwashes have seen a sharp rise in pop- ularity in the commercial market, with claims of antibacterial action, anti-halitosis, caries reduction, and tooth whitening [96]. Research can be conducted on the potential of CQDs in pharmaceutical formulations, as there are still few studies available. Although several applications have been investigated, nothing is known regarding the use of CQDs as labels or tags. Surface passivation, customizable photoluminescence properties, and low toxicity make CQDs a better carrier for labels and tags than semiconductor QDs [9]. For instance, CQDs can be created that are long-term photostable, fluorescent, and non-photobleaching, and can stay in the skin to confirm immunization status. Due to the lack of infrastructure in underdeveloped countries, maintaining vaccination records can be challenging. To overcome this problem, a dissolvable microneedle patch can be used to inject CQDs under the skin and identify vaccination records using near-IR imaging. Individuals with allergies can use similar strategies. Doctors must offer first aid in the event of an accident, and checking for allergic reactions might indicate the difference between life and death before administering medications such as penicillin. Therefore, having CQD tags can help them recognize allergies.

  Next-Generation Carbon-Based Quantum Dots for Healthcare and Beauty Applications · 2026 · DOI

• Future investigations should focus on characterizing oxidative stress responses, assessing DNA repair kinetics, and evaluating replication fidelity to unravel the molecular basis of GQDs-induced genotoxicity. These findings suggest that the genotoxic potential of GQDs is primarily Archives of Toxicology (2026) 100:2355–23661 3 2364 associated with primary DNA lesions rather than structural chromosomal damage or errors in chromosome segregation, but limited to the tested concentration range, exposure dura- tion, and the single 3D HepG2 spheroid model used in this study.

  In vitro toxicity assessment of graphene quantum dots using a 3D HepG2 model · 2026 · DOI

• Carbon Dots as Multi-Modal Contrast Agents: Opportunities and Open Challenges for in Vivo Bioimaging.

  Fe-Doped Carbon Quantum Dots with Magneto-Fluorescent Dual Modality for Fluorescence and Magnetic Resonance Readouts · 2026 · DOI

• In addition, this review addresses important safety and biocompatibility aspects, specifically investigating CD migration and emphasizing that short-term in vitro cytotoxicity tests (often known to show high cell viability) are insufficient as safety tests alone, and that in vivo studies can reveal lethality or chronic toxicity based on surface chemistry.

  Multifunctional carbon dot-based sensors for smart food packaging applications · 2026 · DOI

• Furthermore, the cause of the higher toxicity of CDs in higher concentrations has not been fully explored.

  The Dose-Dependent Effect of Carbon Quantum Dots as a Photosynthesis Enhancer on Soybean Plant Growth · 2025 · DOI

• However, the mechanisms by which the immune system, particularly macrophages, recognizes and responds to these nanomaterials remain poorly understood.

  Involvement of Surface Receptors in the Uptake and Cellular Responses Induced by Cationic Polyamine-Based Carbon Dots in Macrophages · 2025 · DOI

• Developing on-demand biomass valorization represents an ideal path to alleviate the double burden of sustainable energy-environment future, yet exploring tunable lignin-first chemistry to accomplish multifunctional water purification remains elusive.

  Harnessing tunable lignin-based carbon quantum dots for sustainable water purification · 2025 · DOI

• However, currently, there are few reports on the photochromic luminescence phenomenon of CDs, and there is a lack of in‐depth research on the structural design and luminescence mechanism of CDs with photochromic luminescence.

  Surface‐Functionalized Carbon Dots with Photochromic Luminescence in Water and PVA Film · 2025 · DOI

• ABSTRACT Carbon dots (CDs) with photoluminescence properties have been widely recognized; however, their inherent surface‐enhanced Raman scattering (SERS) performance is rarely reported.

  BandGap‐Tunable Carbon Quantum Dots for Surface‐Enhanced Raman Scattering · 2025 · DOI

• Abstract Forestry pests pose serious ecological challenges, yet their biological value remains underexplored.

  Antibacterial activity and wound healing promotion of biomass carbon dots derived from a forestry pest, Glenea cantor (Coleoptera: Cerambycidae) · 2025 · DOI

• While natural carbon dots have been extensively studied for bioimaging, their antibiofilm activity has not been widely explored.

  A Strategy to Combat Bacterial Biofilms Mediated by Plant-Derived Carbon Dots: A Green Shield for Clean Water · 2024 · DOI

• Even though many carbon dots (CDs) based sensors have been developed, few reports on using CDs as optical probes for SCC detection have been published so far.

  Orange carbon dots based smart sensing platforms for rapid, visual, quantitative identification of sodium copper chlorophyllin · 2024 · DOI

• Nanomaterials have demonstrated great potential to enhance photosynthetic efficiency; however, the mechanisms underlying their effects are poorly understood.

  Enhanced photosynthetic efficiency by nitrogen-doped carbon dots via plastoquinone-involved electron transfer in apple · 2024 · DOI

• Despite their photoactivity, it remains unknown whether CDs degrade under illumination and whether such photodegradation poses any cytotoxic effects.

  Photodegradation of carbon dots cause cytotoxicity · 2021 · DOI

• However, the roles and functional mechanisms of CDs and their composite materials in the enhancement of electrochemical performance remain unclear and need to be understood in depth.

  A review of carbon dots and their composite materials for electrochemical energy technologies · 2021 · DOI

• Nevertheless, the synthesis of multicolor solid-state fluorescence (SSF) CDs is rarely reported.

  Construction of Carbon Dots with Color‐Tunable Aggregation‐Induced Emission by Nitrogen‐Induced Intramolecular Charge Transfer · 2021 · DOI

• Future research should focus on the development of new technologies and applications using fruit waste-based nanomaterials. The use of green chemistry for the production of nanoparticles should be further explored. The potential of fruit waste-based nanomaterials in biomedicine, antimicrobial activity, drug delivery, environmental remediation, and food packaging should be further investigated.

  Biological Applications of Nanomaterials Extracted from Fruit Wastes Derived Phytochemicals · 2026 · DOI

• The gap in the current research is the lack of sustainable and eco-friendly approaches to nanotechnology. The use of fruit waste-based nanomaterials can fill this gap. The development of new technologies and applications using fruit waste-based nanomaterials is needed.

  Biological Applications of Nanomaterials Extracted from Fruit Wastes Derived Phytochemicals · 2026 · DOI

Most-cited papers in Carbon and Quantum Dots Applications

• Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection · Science · 1998 · 6,288 citations
• A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors · Environmental Health Perspectives · 2005 · 1,982 citations
• A multifunctional chemical toolbox to engineer carbon dots for biomedical and energy applications · Nature Nanotechnology · 2022 · 1,008 citations
• The light of carbon dots: From mechanism to applications · Matter · 2022 · 959 citations
• Biomass-Based Carbon Dots: Current Development and Future Perspectives · ACS Nano · 2021 · 670 citations
• Photoluminescence mechanism of carbon dots: triggering high-color-purity red fluorescence emission through edge amino protonation · Nature Communications · 2021 · 608 citations
• The development of carbon dots: From the perspective of materials chemistry · Materials Today · 2021 · 540 citations
• Carbon Dots: Synthesis, Properties and Applications · Nanomaterials · 2021 · 504 citations
• Time‐Dependent Phosphorescence Colors from Carbon Dots for Advanced Dynamic Information Encryption · Advanced Materials · 2021 · 488 citations
• Carbon Dots: Classification, Properties, Synthesis, Characterization, and Applications in Health Care—An Updated Review (2018–2021) · Nanomaterials · 2021 · 420 citations

Most recent work

• Lignin carbon dots: Synthesis from alkali lignin, sensing mechanism for Fe3+, performance evaluation, and azo dye composite test paper for dual-mode detection · Biomass and Bioenergy · 2026
• Carbon quantum dots as multifunctional nanomaterials for sustainable optoelectronic biosensing and green photonics · Communications Materials · 2026
• Optical band gap determination of carbon dots: A critical comparison of tangent and Tauc plot methods benchmarked with metal oxides · Carbon · 2026
• Enhanced fluorescence and heavy metal ion sensing using nitrogen-doped carbon quantum dots synthesized from banana peel waste · Results in Engineering · 2026
• Fluorescence-Guided Chitosan and Eugenol-Based Carbon Dots for Comprehensive Infection Control and In Vitro Wound-Healing Applications in Dentistry · Dentistry Journal · 2026
• Flexible and high-color-rendering electroluminescent device via self-adsorptive carbon quantum dots · Journal of Materials Chemistry A · 2026
• Research progress on functional carbon dots for detecting heavy metal ions in the fields of environmental protection and food safety · Talanta · 2026
• Fluorescent sensor approaches for mercury detection: Chemosensors, carbon dots, MOFs, and nanomaterials · Chemosphere · 2026
• Doping-engineered room-temperature phosphorescent carbon dots: Mechanisms, strategies, and applications · Coordination Chemistry Reviews · 2026
• Rare earth-carbon dots hybrids: a critical review of synthetic pathways, energy transfer mechanisms, and advanced photonic applications · Coordination Chemistry Reviews · 2026

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