Recent Biomedical Applications of Carbon Quantum Dots in Cancer Treatment

Abstract

Carbon-based quantum dots (CQDs) have been around for a few decades. Low cell toxicity, good water solubility, excellent and tunable fluorescence properties, and the ability to dope and modify the surface of these CQDs make them an incredible choice for the visualization and treatment of various cancers. This perspective analyzes some recent progress on size-color correlation, modification, and cancer treatment applications of CQDs. Synthesis and modification of CQDs to make them more efficient and more biocompatible are essential to their bioapplications.

Graphical Abstract

Introduction

A material’s color and its photoluminescent/fluorescence emission color in the ultraviolet (UV) to infrared (IR) region are determined by its electronic quantum energy structure, which is largely due to the electron motions in the materials locally among connected atoms and delocalized wave-diffusively among many layers of atoms, according to the molecular orbital theory and bandgap theory.^1,2 Quantum dots have bright fluorescence emissions under illumination whose color can be tuned by the size of the dots. The quantum confinement effect in carbon-based materials was expected after semiconductor quantum dots with a leading composition CdSe were synthesized and reported in 1982 and won the Nobel Prize in Chemistry 2023.³ The energy bandgap of the material determines the color of it. Quantum dot color represented by its emission peak wavelength is related to the bandgap of the bulk material and is approximately corrected by the quantum particle-in-a-box equation originally proposed by Nobel Laureate Dr. Louis Brus,⁴

$$\Delta E_{\text{QD}}=\Delta E_{\text{bulk}}+\frac{a}{r^2}$$ (1)

where ΔE_QD is the bandgap energy of the quantum dot, ΔE_bulk is the bandgap of the material in large crystal bulk form, a is roughly a constant related to the atomic environment of the electron-hole motion in the particle, and r is the effective radius of the particle.

The quantum confinement effect of electrons and holes in a typical semiconductor material is correlated with their de Broglie wavelength at typically <10 nm. Quantum dots that are smaller than this size squish the wavefunctions of electrons and holes to larger energy gaps. For example, for CdSe, the bandgap of bulk material is 1.74 eV with photoluminescent emission at 1240/1.74 ≈ 710 nm, and $a=0.96 eV*n{m}^2$ fitted for experimental data from a CdSe vendor (Figure 1).^5–7

Figure 1.

(a) Jablonski energy diagram and (b) fitting of CdSe quantum dot photoluminescence emission peak energy over its effective particle radius. Data courtesy from NN-Labs^5,7 (acquired in July 2024).

A better fit to the experimental data can be obtained by adding a b/r term to represent other interactions such as the electron-hole interactions,⁸

$$\Delta E_{\text{QD}}=\Delta E_{\mathit{\text{bulk}}}+\frac{a}{r^2}+\frac{b}{r}$$ (2)

The above same experimental data yields a fit with a = 0.43 eV×nm², and b = 0.44 eV×nm. This equation fits the emission peak more accurately (Figure 1). For example, a spherical CdSe QD with a 4.0 nm diameter has an effective radius of 2.0 nm and a bandgap of ~2.1 eV, whose photoluminescent emission can be found at ~590 nm wavelength, in orange color.

For carbon-based nanomaterials, scientists were more interested in nanotubes and fullerene-related carbon materials before 2006.⁹ Other carbon dots gained attention after carbon dots with the full visible emission spectra were synthesized in 2006 which immediately seems comparable to the established CdSe quantum dots at that time.¹⁰ These carbon dots were aggregates of nano-sized graphene or graphite with various surface functional molecules whose fluorescence mechanism has been reviewed.^11,12 Briefly, chemical modification is achieved intrinsically during synthesis or post-modified by attaching functional groups. Physical passivation is achieved by surfactants, polymers, and ceramic materials with core-shell architectures. Graphene is an allotrope of carbon that can be described as a monolayer of carbon atoms arranged in a hexagonal lattice structure. It is extremely strong while having exceptionally low mass-volume density. Multiple layers of graphene can be combined to form graphite.

Bare carbon materials are known to have low water solubility and minimal fluorescence whose emission is quenched by water, releasing heat. As such, electronic passivation is necessary to observe photoluminescence. Chemical modification is also needed to increase water solubility because bare CQDs and graphene are hydrophobic.

Proper passivation is a prerequisite of photoluminescence for atomic emitters such as Erbium, various organic dye molecules, and nanoparticles such as QDs and gold nanoparticles, probably because some passivation methods suppress the Dexter charge transfer from CQDs to solvent molecules. This quenching mechanism has been observed in some organic dyes quenched by solvents, especially for polar solvents that have a strong dipole-dipole interaction with the emitters.^13,14 Due to the structural similarities of CQDs with both small organic dyes such as aromatic compounds and bulk carbon materials such as graphene, CQDs close the gap between the molecular orbital theory for small organic dyes and the bandgap theory of bulk materials.

In general, the applications of nanomaterials in industries are motivative topics in chemistry. As more research becomes available, more light is shone upon the applications of these small particles. Much of the interest in nanomaterials, specifically quantum dots, is rooted in biomedical applications. QDs have chemical, physical, and economic benefits in these areas. The number of publications containing the term “carbon dots” has grown exponentially in the past decade and reached ~2000 articles plus ~300 reviews and book chapters per year in 2023, according to the Scopus database, accumulating respectful ~13,000 documents in total March 2024. Conservably assuming an equivalent $50,000 fund per publication, it suggests that over half a billion US dollars of funds have been spent in related research fields. This attention is mainly motivated by the race to commercialize CQDs in various applications such as light-emitting diodes (LEDs), lasers, voltaic devices, photoconductors and photodetectors, catalysts, biolabeling, and cancer treatment, which has been prospected in many review articles.^11,15–21

CQDs are superior to traditional organic dyes in bioimaging performance but are larger than typical small organic molecules and thus are more difficult to deliver or remove in body tissues. In addition, carbon-based nanomaterials are easily modified to have higher solubility in aqueous solutions, are chemically inert, and are highly resistant to photobleaching. It has also been found that they have a low toxicity and substantial biocompatibility, further cementing their use as biomedical sensors, image markers, and delivery vehicles.^{9,12,19,22–24} It is not surprising that scientists and labs across the world are attempting to perfect the synthesis of these outstanding particles.

Authorities in many countries have recently approved human clinic trials for QDs. For example, the U.S. Food and Drug Administration (FDA) approved the first clinical trial in 2011 for quantum dots in human biomedical imaging. These are silicon quantum dots named Cornell dots or C dots that are fluorescent and brighter than unencapsulated organic dyes. After three human clinical trials, its safety concern has reduced. C dots moved into the therapeutic trials in 2021.²⁵ Carbon is typically considered a safe material with proper surface modification thus we may see an increase in clinic trials for carbon nanoparticles.²³ ClinicalTials.gov accessed March 2024 listed 18 human clinic trials mostly in China targeting various tumor treatments.²⁶ We will review the recent progress of carbon dots in cancer treatment in the literature.

Synthesis and optical properties

As with any new scientific discovery, there is a large amount of attention to how various synthetic methods can be used to achieve the ideal nanoparticles. Once a general synthesis method is determined, the goal of making the technique more economical and eco-friendly takes precedence. Changing the synthetic means could also change the properties and therefore the applications of the particles. CQD synthesis involves many different techniques and sources of carbon atoms. Depending on the desired properties, particles can also be doped with other elements, primarily transition metal ions or nonmetals such as sulfur and nitrogen. The addition of these atoms to traditional CQDs changes the optical properties of the nanoparticles. For example, nitrogen doping is particularly interesting due to its success in bulk graphene.²⁷

There are many techniques used to synthesize CQDs. The two common means of generating CQDs involve either a top-down or a bottom-up approach as has been summarized in the literature including many review articles (Figure 2).^{9,16,18–22,28–33} Most methods yield aggregates or clusters of CQDs with sizes that appear to be larger than that of the individual particles. CQDs aggregate into clusters due to the strong van der Waals interactions between the particles. As such, the sizes of CQD particles are relatively randomly distributed in the literature and typically <10 nm to maintain the name quantum dots. The individual carbon particles/domains/grains assuming graphene that emit in the visible region are expected to be <2 nm,^34,35 a few times larger than gold quantum dots with similar colors.³⁶

Figure 2.

(a) Scheme of top-down versus bottom-up approaches to forming graphene quantum dots. Reproduced with permission from ref.³³, copyright 2021 American Chemical Society. (b) Scheme, photos, UV-Vis absorption and photoluminescent spectra, and infrared spectra of CQDs. Reproduced with permissions from¹⁰, copyright 2006 American Chemical Society; and³⁷, copyright 2020 Elsevier. (c) Transmission electron microscopy (TEM) images CQDs passivated with amino acids. Reproduced with permissions from³⁸, copyright 2024 American Chemical Society.

One of the original approaches employed as a byproduct of purifying single-walled carbon nanotubes using electrophoresis.^18,22,39 Another method is focused on the fact that strong acids can reduce small organic molecules into compounds containing carbon atoms. These small compounds can be further treated by controlled oxidation which leads to the formation of CQDs.^18,22,40 In a top-down approach, a source of pure-carbon material, such as graphite, carbon nanotubes, graphene oxides, or nanodiamonds, is broken down into super-small particles, forming carbon dots. A bottom-up approach requires using compounds that can be broken down into individual ions and radicals as a source of carbon atoms. These carbon atoms can then be used to form the CQDs.⁴¹ The pioneer method incorporates a top-down approach to breaking carbon nanotubes into smaller CQDs while the chemical ablation uses more of a bottom-up approach.

Other examples of a top-down approach are arc discharge, laser ablation, and electrochemical synthesis while bottom-up approaches include combustion, hydrothermal or solvothermal methods, and microwave irradiation of chemicals or natural products. For example, foods,^37,41–48 and plants^29,49–52 are particularly attractive sources containing active carbon compounds such as polyphenols, flavonoids, carotenoids, sugars, polysaccharides, cellulose, hemicellulose, and lignin, and other elements such as oxygen, nitrogen, sulfur, phosphorus, that may dope in the CQDs during synthesis or provide functionalization to the CQD surface. Generating carbon materials such as soot and charcoal from these sources is a traditional green synthesis method. The chemical complexity of such sources and their effects on the surface functionalization of the CQDs make green synthesis an actively explored field.

Doping is a particularly interesting process for CQDs where impurity elements replace carbon atoms in the graphene or diamond lattice. Lattice doping is different from surface functionalization when edge carbons are modified by functional groups such as −OH, −COOH, −NOx, −Sox via chemical bonds, and passivated by other molecules such as polymers via mainly van der Waals forces. Doping significantly changes the bandgap of CQDs, for example, nitrogen doping or surface functionalization red shifts its adsorption and emission peak via n-π* transitions in the molecular orbitals.^27,53,54 Natural nitrogen compounds in the synthetic precursor or additives, such as ethylene diamine, ammonia, or urea and cysteine provide nitrogen sources to the doping.^24,27,54,55

The emission peak of CQDs assuming graphene can be calculated using density functional theory (DFT) and some results are shown in Figure 3. An experimental measurement of CQDs with known size is consistent with the trend of the DFT calculations. These data can be fitted with Equations 1 and 2 as an estimation of peak and size correlation using bulk graphene bandgap ΔE_bulk = 0 eV. Interestingly the bandgap energies from the DFT calculations follow an inverse correlation with radius, while the square inverse can only fit part of the data. From these calculations, we can see that for CQDs to have emission in the visible region, individual particles should be smaller than 1.5 nm in diameter. Many measurements of CQDs with atomic force microscopy (AFM) show a height <1.5 nm^11,53,56 which lands in the visible region as estimated but it is not known if these heights are the single particle sizes or just the heights of a few layers of graphene. If the emission is from inter-layer electron motion and/or significantly shifted by doping,⁵³ the energy gap of multi-layer graphene and effect doping can be further calculated.

Figure 3.

Fitting of emission peaks over graphene QDs calculated from DFT (Data of red dots are acquired from ref.³⁴, blue dots from ref.⁵⁷) and experimental measurement of one CQD are acquired from ref.³⁵ (green dot). Effective radius r is estimated from area A = πr² (lower left inset), using C-C bond length 0.142 nm thus the area of each hexagonal unit is 0.052 nm², and each atom 0.013 nm².

The aggregated particles observed under transmission electron microscopy (TEM) typically are >5 nm in diameter.^34,56 However, particle height measured by AFM is smaller, and the size estimated from the molecular weight of the CQD particles is much smaller than 5 nm in diameter as well. For example, typical CQDs with strong visible emission have molecular weight <3500 Dalton cut-off in dialysis, and some are measured using mass spectrometry.^11,34 CQD with 3500 Da molecular weight has 290 carbon atoms. If they form a single-layer graphene sheet 2D material, it will have ~3.8 nm² in area or 2.2 nm in effective diameter. It is possible that TEM images miss the single-layer graphene ones and pick the aggregated ones due to the difficulty of seeing graphene under TEM. These samples are typically deposited on carbon films for TEM imaging thus a threshold thickness is needed to be distinguished from the carbon film background. Recent TEM measurements have started to pay extra attention to observing the CQDs <3 nm in diameter.^58,59

Size is important because bigger particles are more difficult to remove from bodies and may accumulate to cause long-term chronic health concerns. Progress in the metabolism of CQDs in the body has been reviewed, suggesting an upper limit of size to be removed from body due to their high chemical stabilities in bodies.³¹ Several reports have shown that CQDs <6 nm have rapid renal excretion but >8 nm is much slower to remove.

Biomedical applications

Among nanomaterials, QDs and polymer dots (Pdots)^60,61 are competing in biomedical applications, both have tunable colors in the visible and near-infrared regions and have compatible sizes. Typically, Pdots are a little larger than QDs. Once the potential of material in medical applications is identified, careful investigation of biocompatibility, cytotoxicity, and metabolism in cells and animal bodies must follow before moving it into clinical trials.^28,31,62 For bioimaging, a particularly important parameter is the selectivity to a particular area of cells, e.g. nuclear, mitochondria, and cell walls, and specific cells such as cancer cells. Some CQDs obtained from various sources and methods show minimum toxicity to normal cells during cancer tumor labeling.^63,64

Cytotoxicity

The progress of CQD cytotoxicity has been reviewed.^{16,21,23,28,31,33} A conclusion is that they are much less toxic than traditional QDs such as CdSe and CdS QDs. Low toxicity of CQDs is observed at low in vivo concentration at a few mg/kg. While carbon materials are generally believed to be nontoxic, size, the toxicity of their surface functional groups, toxic impurities in the final solutions, photo-induced reactive oxygen species (ROS), and photodegradation products are carefully studied.

Early-state examination of CQD cytotoxicity is usually done with in-vitro cell viability assays before the animal models are introduced. Most more recent reports (than those reviewed) show safe results of in-vitro assays for CQDs. For example, cytotoxicity of a nitrogen- and sulfur-doped CQD is tested using SVG p12 normal brain cells;⁵⁵ nitrogen-doped CQDs synthesized from lotus root are tested using A549 lung cell line;⁵¹ CQDs formed from neem tree, holy basil, and tridax daisy, range from 6–10 nm in size are tested under MCF7 human breast cancer cell lines and Hela cervical cancer cell lines.^29,52 An example is given in Figure 4 for the cytotoxicity test of CQDs using MTT and WST-1 cell viability assays where low cytotoxicity is observed at <1 mg/mL.⁶⁵

Figure 4.

An example MTT/WST-1 cell viability assay using human Mesenchymal Stem Cells (hMSC) for two CQDs synthesized from a colloidal method comparing to a commercial graphene quantum dot (GQD). Reproduced from ref.⁶⁵, copyright ACS 2023.

CQD functionalizations

In addition to the functionalization of CQDs for better water solubility, biocompatibility, and electronic passivation for photoluminescence, functionalizations to selectivity deliver CQD to target tissues, organs, or locations are required for in vivo applications. CQD functionalizations have been well-reviewed in the literature.^{16,18,19,21,28,55,62} Endocytosis is a major cell wall penetration mechanism for nanoparticles which is initialized by the selective binding of the nanoparticle to the cell walls.^66,67 Using assorted carbon precursors can lead to many types of atoms and functional groups bonded to the surface of the CQDs without the need for additional surface passivation.^{16,19,22,30,32,68} CQDs, particularly graphene nanosheets, have rich edge carbon atoms that are readily compatible with various organic synthesis methods to attach functional groups, such as −CH₃, −OH, −COOH, −NH₂, NO₂, −SO₃H, and −OPO₃H₂.⁶⁹ Thus, edge modification is relatively straightforward. Doping and selective lattice functionalization have a more complicated effect on the properties of CQDs.³⁰ A particularly interesting opportunity for CQD modification is using hydrophobic interactions and van der Waals forces between CQDs and functional molecules because CQDs typically have larger sheet areas than small molecules and are hydrophobic at the sheet surface. All these strategies have shown promise in drug delivery and selective biolabeling.

The tumor selectivity after CQD injection can be achieved via the enhanced permeability and retention effect tumor cells naturally have. Once enters a cancer cell, CQDs can further target lysosomes or nuclei. Two examples of selective tumor labeling are given in Figure 5 and Figure 6 indicating the concentrating of CQDs in tumor and a few other organs.⁷⁰ Even if the load is similar between normal and cancer cells, high-concentration metabolic products in cancer cells can be used to enhance the fluorescence signal of CQDs. For example, cancer cells have a higher concentration of desmin and a higher rate of reduction from Fe³⁺ to Fe²⁺ than normal cells. Desmin can be used as a biomarker for CQD tumor sensing;⁷¹ Fe²⁺ can increase the fluorescence of CQDs as seen in cancerous A549 and HepG2 cells.⁷²

Figure 5.

An example study of mouse tumor labeling with CQDs. (a) Photos and fluorescent images of a mouse with a tumor under the arm after the injection of a CQD solution (5 mg/kg). (b, c) Selectivity of CQD delivery to the tumor. Inset of (c) showing the photo of the CQD solution and proposed possible structure. Reproduced from ref.⁷⁰, copyright 2020 American Chemical Society.

Figure 6.

(a) Fluorescence imaging of mice with tumor induced by Smmc-7721 cells after being injected with CQDs compared to (b) the fluorescence imaging of the dissected organs of the mice 24 hours after injection indicating the concentrating of CQDs in kidney, liver, and tumor. Reproduced from⁷³. Available under a CC BY 4.0 license. Copyright Qiang Yong.

Active delivery strategies have been proposed and their progress has been reviewed in the literature.^74,75 An example is given in Figure 7 using selective binding functionalizations.⁷⁶ Both the edge functionalization and hydrophobic attraction are used to add multiple functions such as selective binding to target cells and drug loading to the CQD center. Other selective targeting compounds have been tested. For example, both E- and P-selectins are molecules that are resultants of inflammation and are found in high concentrations in cancerous tissues.⁷⁷ Molecules that carry carboxylic acid groups, such as quinic acid⁷⁷ and folic acid³⁷ have high affinities to selectins and have been proposed for cancer treatment. Gemcitabine (Gem), a chemotherapy drug, is attached to the quinic acid modified CQDs and is then injected into the tail of mice both with and without tumors. The overall cytotoxicity of quinic acid modified CQDs carrying a chemotherapy drug Gemcitabine (Gem) is found compatible with Gem alone in a cell viability assay.⁷⁷

Figure 7.

Proposed structure of a molecule containing carbon quantum dots that have been modified with polyethylene glycol (PEG), the targeting ligand riboflavin (RF, vitamin B2), an anticancer drug with benzofuran structure (BFG). Reproduced from reference⁷⁶. Available under a CC BY 4.0 license. Copyright Daniela Iannazzo.

Photothermal therapy

The passive delivery strategy can be further used in the photothermal therapy of cancers. CQDs are much more stable than organic molecules and resist photobleaching. Thus, it is a good candidate for photothermal therapy as a close competitor to polymer dots and small molecules.^78,79 Such applications prefer near-infrared light absorption in order to excite deep tissues. Because emission is not required and in fact should be suppressed, CQD electronic passivation is not needed for such applications, but biocompatible functionalization is still needed. Several recent animal studies have shown promising photothermal cancer treatment with an example given in Figure 8. These CQDs were synthesized to have strong light absorption at 808 nm but poor photoluminescence.⁸⁰

Figure 8.

An example photothermal theory experiment of cancer in mice. (a) Photos of tumors, (b) size of tumors under control and photothermal therapy treatment with 808 nm laser light (red), (c) mice health monitored by body weight, and (d) images of mice. Reproduced from reference⁸⁰, copyright 2021 American Chemical Society.

Paired with other anti-cancer drugs

CQDs can be paired with chemotherapy drugs jointly for various cancer treatments, particularly, CQDs’ photothermal efficiency can be further increased using photosensitizers. As an example, red-emitting carbon dots (RCDs) were linked to a photosensitizer Chlorin-e6 (Ce6) so that both photothermal therapy and photodynamic therapy can be completed at the same time.⁸¹ The example thermal images of mice injected with CQD conjugated with Ce6 are shown in Figure 9. This conjugation helps to simplify the tumor-killing process as Ce6 by itself is not good at targeting tumors, has issues with phototoxicity, and aggregates in water. When mixing with CQDs, these issues are reduced or overcome.

Figure 9.

(a) Thermal images of a mouse with a tumor on the right bottom area injected with Ce6-modified red-emitting CQDs (RCDs-Ce6) under 655 nm laser (500 mW/cm²). (b) The heating curves of the tumors after administrated with RCDs-Ce6 for 0, 2, 8, and 24 h. Reproduced from ref.⁸¹ copyright 2023 Elsevier.

Various cancers have been studied for CQDs in the literature besides the above-mentioned examples. For example, CQDs show a similar cytotoxicity level to the current breast cancer chemotherapy drug Paclitaxel.⁸² CQDs coupled with doxorubicin (Dox) show promising potential in photothermal therapy of breast cancers.^83,84 Dox is an anthracycline type of chemotherapy that is used to treat several different types of cancer.

Similar to how Dox can be used to treat breast cancer and therefore linked to CQDs for a more targeted delivery and treatment, imatinib is another chemotherapy drug that helps to control cancer cell growth by blocking the signal that tells the cells to multiply. It works on many diverse types of cancers but is generally used for the treatment of leukemia. When imatinib is coupled with CQDs, there is mild cell death when compared to untreated human myeloma cells (RPMI 8226).⁸⁵ The cytotoxicity of the modified CQDs was less than that of pure imatinib without the presence of the nanoparticles. The decrease in cell toxicity when the chemotherapy drug is decorated on the quantum dots is hypothesized due to a delay in the release of the medication or due to a disassociation of the anticancer molecule.⁸⁵

Chlorophyll-based CQDs were tested on HEK-293 and SiHa cells.⁸⁶ HEK-293 is a cell line that consists of renal epithelial cells while SiHa is from a uterine squamous cell carcinoma or a cervical cancer tissue. The CQDs slowed the proliferation of the cancer cells while not showing any cytotoxic effects on the normal kidney cells. Along with this impediment of cell growth, the CQDs also promoted a change in the nuclei of the SiHa cells which led to apoptosis.⁸⁶ No apoptotic or necrotic cells are present in the normal HEK-293 cells after being treated with the CQDs for over 24 hours suggesting that they are biocompatible with healthy cells.

Due to the complexity of CQDs in size, composition, and functionalization inherited from various preparation methods, plus the impurities in various synthetic and purification solutions, the more carbon quantum dots are studied in regard to the treatment of cancer, the more convoluted the data can become. There are some instances where the CQDs increase the cell death rate of cancerous tissue and others where the chemotherapy medication is more effective on its own. It can also depend on the specific CQDs that are being used and their individual properties. This is maybe even more important when the nanoparticles are being used on their own instead of in conjunction with any type of anticancer drug. When testing the cell viability of two distinct types of mouse cancer cell lines such as colon (C26) and bladder (MBT-2) carcinomas, blue emitting CQDs are more biocompatible with the C26 cells and green emitting CQDs are more biocompatible with the MBT-2 cells.⁸⁷ This means that the specific photoluminescence properties of the quantum dots can impact the cytotoxicity of them against cancer cells. The CQDs that are more biocompatible with each type of cancer cell line are less likely to kill those cells and are therefore less effective.

Conclusions

For CQD preparation, we are expecting to see more synthesis, separation, purification, and modification reports in the future and more accurate measurements of the individual particle sizes, leading to more uniform sizes and narrower emission bands. We should also see more calculations of the bandgaps of CQDs. Particularly important is to understand the effects of doping in breaking the continuity of the electron paths which induces bandgap splitting of graphene, multilayer graphene interactions, and the effect of surface passivation in water on their photoluminescence properties. The current synthetic strategy is mainly via trial and error with some rough rationales, this is why so many different sources and routes have been reported. Theoretical calculations and modeling powered by quantum calculation, molecular dynamic simulations, and machine learning may in the future provide clearer guidelines.

Surface functionalizations and their cytotoxicity will continue to be a key research area for CQDs. All quantum dots are excellent sources of color reagents for non-clinical or in-vitro applications. If the safety concerns of CQD are further reduced, they will certainly move into clinical trials in various disease treatments, especially cancer treatment. Because the chemical composition of CQDs is complicated due to the relatively large number of atoms in it, purification, and characterization remain challenging. In addition to the widely used TEM and FTIR/Raman, we may see more characterizations using methods such as Mass spectroscopy, NMR, and various spectroscopies and microscopies especially at the single-particle level.

The complicity of surface functionalization also makes it challenging to identify the cytotoxicity of each functional group. The luminescent domains in such particles should be <2 nm to land their absorption into the near infrared region. Observing such small particles, finding their chemical compositions, synthesizing more uniform ones, and correlating CQD properties to cytotoxicity remain challenging. In the clinical trials, another particularly challenging and important evaluation is the long-term side effect of CQDs, for which getting uniformly small size <6 nm in diameter for each particle/cluster/composite seems to be one of the key requirements. We expect to see more in-vivo experiments and clinical trials of CQDs in human bodies such as tumor labeling, photothermal treatment, and as co-reagents and carrier vehicles for other chemotherapy drugs.

Biographies

Credit:

Jenna L. Mowery is a Chemistry Teacher at Midd-West High School, a secondary public school in Middleburg, Pennsylvania. She earned a bachelor’s degree in chemistry from Susquehanna University (Selinsgrove, Pennsylvania) in 2018. She then earned a M.S. in chemistry from Ohio University (Athens, Ohio) in 2023. Ever since taking a Nanoscience course in her undergraduate studies, Jenna has enjoyed the realm of quantum dots and the like. This perspective article is based on her senior manuscript at Ohio University. When not teaching others chemistry, she enjoys reading and relaxing with her family (her husband Tyson and their son Tanner), friends, and pets.

Credit: Jixin Chen

Jixin Chen received his B.S. and M.S. degrees in Chemistry from Nankai University, Tianjin and Ph.D. degree in Chemistry from Texas A&M University, College Station. He carried out postdoctoral research at the University of Wisconsin, Madison and Rice University, Houston before joining Ohio University at Athens as an assistant professor. His research is single-molecule and single-particle kinetics.