Excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria

Excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 10 June 2025 V1 Latest version Share on Excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria Authors : Chukavin N. N. 0000-0001-8431-4485 [email protected] , Popov A. L. , Viktoriia Anikina 0000-0002-5028-2064 , Дарья Винник 0009-0004-8978-6923 , Bokl B. A. , and Popova N. R. Authors Info & Affiliations https://doi.org/10.22541/au.174954473.33624714/v1 Published Toxicology in Vitro Version of record Peer review timeline 229 views 155 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Curcumin is a natural bioactive substance with promising biomedical applications. However, the low solubility and stability of curcumin significantly limit its potential use. The development of nanoformulations of curcumin makes it possible to circumvent the above limitations. Cerium dioxide (CeO 2 , NDC) nanoparticles are a promising platform for curcumin binding. They are able to absorb curcumin on their surface, providing increased bioavailability and bioaccumulation. Moreover, NDC have unique enzyme-like properties that can be used for targeted delivery and controlled release of curcumin. Meanwhile, the potential cytotoxicity of such nanoformulations remains poorly understood. In this work, we synthesized the NDC-curcumin nanoconjugate and investigated the effect of excess curcumin on the cytotoxicity of this nanoformulation. Curcumin has been shown to bind to the surface of nanoparticles, forming a sustainable and colloidally stable nanoconjugate. At the same time, excess curcumin formed a separate colloidal nanoscale fraction, which caused the pronounced cytotoxicity of the nanoconjugate in relation to human immortalized keratinocytes (HaCaT), primary mesenchymal stem cells (hMSc) and fibroblasts (HF). In turn, NDC provided an increased biocompatibility of curcumin. Thus, the application of a rational design of curcumin nanoformulations will help to overcome possible limitations of its use in practice and maximize its bioactivity. Cite this paper: Chin. J. Chem. 2024 , 42 , XXX—XXX. DOI: 10.1002/cjoc.202400XXX Excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria Chukavin N. N., a,* Popov A. L., a Anikina V. A., a Vinnik D. A., a Bokl B. A., a and Popova N. R. a a Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, 3 Institutskaya St., Pushchino, Russia, 142290 Curcumin | Nanoceria | Cytotoxicity | Nanoconjugate Comprehensive Summary Curcumin is a natural bioactive substance with promising biomedical applications. However, the low solubility and stability of curcumin significantly limit its potential use. The development of nanoformulations of curcumin makes it possible to circumvent the above limitations. Cerium dioxide (CeO 2 , NDC) nanoparticles are a promising platform for curcumin binding. They are able to absorb curcumin on their surface, providing increased bioavailability and bioaccumulation. Moreover, NDC have unique enzyme-like properties that can be used for targeted delivery and controlled release of curcumin. Meanwhile, the potential cytotoxicity of such nanoformulations remains poorly understood. In this work, we synthesized the NDC-curcumin nanoconjugate and investigated the effect of excess curcumin on the cytotoxicity of this nanoformulation. Curcumin has been shown to bind to the surface of nanoparticles, forming a sustainable and colloidally stable nanoconjugate. At the same time, excess curcumin formed a separate colloidal nanoscale fraction, which caused the pronounced cytotoxicity of the nanoconjugate in relation to human immortalized keratinocytes (HaCaT), primary mesenchymal stem cells (hMSc) and fibroblasts (HF). In turn, NDC provided an increased biocompatibility of curcumin. Thus, the application of a rational design of curcumin nanoformulations will help to overcome possible limitations of its use in practice and maximize its bioactivity. Background and Originality Content Curcumin is a hydrophobic polyphenol found in Curcuma longa rhizome extract. This substance has a wide range of proven biological activities [1–3] . In particular, curcumin has been shown to have an anti-inflammatory effect by reducing the expression of inflammatory mediators [4–6] . The biological activity of curcumin is determined by the peculiarities of its chemical structure, which includes two aromatic rings functionalized by hydroxy and methoxy groups interconnected by a spacer of two α,β-unsaturated carbonyl groups. This structure allows the existence of beta-diketone and keto-enol tautomeric forms of curcumin [7] . It has been shown that due to the peculiarities of the chemical structure, curcumin is able to interact and bind with various biomolecules, affecting their activity and modulating signaling pathways in the cell [8, 9] . At the same time, curcumin is characterized by extremely low solubility in hydrophilic media, low stability and bioavailability, and is rapidly metabolized and excreted from the body [10–13] . However, there are approaches that make it possible to overcome the above limitations. One of these approaches is the development of co-crystals with improved physico-chemical properties and increased stability [14] . The previously developed curcumin co-crystals demonstrated a reduced melting point and increased solubility [15–18] . There are also approaches for the delivery and stabilization of curcumin using various nanoformulations and nanoconjugates, based on liposomes [19] , exosomes [20] , micelles [21–23] , nanoparticles [24, 25] and dendrimers [26] . Thus, curcumin is a biologically active substance with significant potential for biomedical applications, which can be effectively used as a functional ligand together with its stabilizing nanoformulation. Cerium-based nanoparticles (nanoceria) can act as an effective platform for binding curcumin. These include cerium dioxide (CeO 2 , hereinafter NDC) nanoparticles capable of mimicking the activity of natural enzymes such as superoxide dismutase, oxidase, catalase, and peroxidase [27, 28] , photolyase [29] , phospholipase [30] and nuclease [31] . The enzyme–like activity of NDC is due to the structural features of the crystal lattice of nanoparticles, the presence of Ce 3+ and Ce 4+ ions and defects in its composition, called oxygen vacancies, and manifests itself depending on the configuration of nanoparticles and microenvironment conditions [32–34] . This, in turn, determines their bioactivity. In particular, NDC can exhibit an anti-inflammatory activity by reducing the expression of pro-inflammatory factors [35, 36] . Cerium fluoride (CeF 3 ) nanoparticles are also nanoceria. They have redox activity [37] , due to which they are able to selectively modulate the cellular response to X-ray irradiation [38] , and can also be modified for luminescent imaging [39] . At the same time, CeO 2 and CeF 3 nanoparticles exhibit radioprotective properties in relation to Schmidtea mediterranea under X-ray irradiation conditions [40] . In addition, both types of cerium nanoparticles demonstrate a synergistic antimicrobial effect with cold atmospheric plasma [41] . Thus, nanoceria represents a promising platform for biomedical applications. Modification of the cerium dioxide nanoparticles with functional elements makes it possible to obtain nanoformulations with improved or new properties. The conjugate of NDC and calcein has a unique feature of detecting the level of intracellular reactive oxygen species (ROS) along with their neutralization [42, 43] , whereas the NDC-mildronate composite exhibits mitochondrially targeted radioprotective activity [44] . Nanoformulations of NDC and doxorubicin [45] , TNF-α [46] , ssDNA [47] , inhibitor of Hsp90, doxorubicin and folate [48] , labeled dsDNA [49] , chitosan, ZM241385 and pilocarpine [50] , clindamycin [51] , morin [52] , FITC [53] and miRNA-146a [54–56] , as well as NDC doped with gadolinium [57, 58] , are also known. Approaches to creating nanoformulations of curcumin based on nanoceria are being actively developed. The binding of these components is achieved through the formation of hydrogen bonds between them and the formation of chelate complexes. [59] . Among the various methods of curcumin binding using NDC, those based on polysaccharide stabilization [60] , incorporation into biopolymers [61] , hydrogels [62] and extracellular matrix [63] , binding by phospholipids [64] , encapsulation in copolymers [65] , coordination by polypeptides [66] and formation of nanoconjugates with curcumin in colloidal form [67] . These nanoformulations show a wide range of bioactivities, such as anti-inflammatory, antioxidant, and wound healing effects, as well as selective antitumor activity. This opens up prospects for their use in the treatment of oncological and chronic inflammatory diseases. However, the potential cytotoxicity of such nanoformulations remains poorly understood. In this paper, we investigated the effect of excess curcumin on the cytotoxicity of its nanoconjugate with nanoceria (Figure 1). Figure 1 The exisitng problem of curcumin practical use (a), current approaches to increase curcumin bioactivity by nanoceria-based formulations (b), and the problem of possible cytotoxicity of such nanoformulations, uncovered in this work (c). Results and Discussion The NDC-curcumin nanoconjugate was formed in 96% ethyl alcohol by mixing NDC sol and curcumin solution in the presence of PVP as a stabilizer, then dried and redispersed in deionized water. It should be noted that cerium dioxide nanoparticles actually form a hybrid nanoformulation with curcumin. First, when a light-yellow curcumin solution was added to a milk-white NDC sol, the final NDC-curcumin colloidal solution acquired a dark-orange color (Figure S1). Moreover, the optical absorption spectra of the nanoconjugate components have undergone significant changes: the absorption of both components in the UV region has increased nonadditively, and the peak of curcumin absorption has expanded to the long-wavelength region (Figure 2b). This indicates a change in the electronic configurations of NDC and curcumin due to the formation of a stable nanoconjugate structure. The absorption spectrum of the nanoconjugate remained unchanged after 2 weeks of storage, which further confirms the stability of the resulting nanoformulation. At the same time, the nanoconjugate demonstrated a hydrodynamic size of about 30 nm, exceeding the size of the NDC by 5 nm (Figures 2d and S2a). This phenomenon can be attributed to the formation of a layer of molecular curcumin on the surface of nanoparticles. The binding of curcumin also caused a significant change in the zeta potential of the NDC: the charge of the nanoparticles changed from positive (+25 mV) to negative (-23 mV) values (Figures 2e and S2c). All the above results give substantial grounds to assert that the synthesized sample of NDC-curcumin is an integral organo-inorganic nanoconjugate, not a simple mixture of components. Presumably, curcumin binds to NDC by forming coordination bonds between carbonyl groups of curcumin and Ce 4+ ions exposed on the surface of nanoparticles (Figure 2a). As a result, the positive charge of cerium ions is leveled, the zeta potential of nanoparticles is reversed, the nanoparticles increased in hydrodynamic size, and the electronic configuration of both components changed significantly. Meanwhile, in addition to the monodisperse fraction of NDC-curcumin itself, a polydisperse fraction of excess curcumin was found in the nanoconjugate sample (Figure 2c), which was absent in the non-functionalized NDC sample (Figure S2b). This fraction is colloidal curcumin, which is not bound to NDC, but is stabilized by PVP, and has a particle size from 50 to 100 nm. Figure 2 The proposed scheme of binding of cerium dioxide nanoparticles (NDC) and curcumin (a). Absorption spectra of curcumin, NDC and NDC–curcumin nanoconjugate before and after storage for 14 days at 4 ° C, as well as the summarized absorption spectra of NDC and curcumin (b). Scanning electron microscopy (c), distributions of hydrodynamic diameter (d) and zeta potential of the nanoconjugate (e). The NDC-curcumin nanoconjugate demonstrated a high degree of biocompatibility with respect to HaCaT cells at concentrations up to 250 µM (here and further, the concentration is indicated by cerium for NDC alone and NDC-curcumin and by curcumin for curcumin alone), similar to the effect of NDC (Figure 3a). However, when these cells were coincubated with the nanoconjugate at a concentration of 500 µM, a statistically significant decrease in their viability was observed after 24 hours, and after 72 hours the percentage of dead cells reached almost 50% (Figure 3b). This effect correlates with the cytotoxicity of curcumin alone, which was even more pronounced. It is suggested that the cytotoxic effect of the nanoconjugate is due to the presence of an excess curcumin fraction in the sample, which was previously detected during a physico-chemical analysis. Figure 3 Cell viability (a) and dead cell percentage (b) of immortalized human keratinocytes of the HaCaT line after 24, 48, and 72 hours of coincubation with NDC, curcumin and NDC-curcumin nanoconjugate in concentrations from 10 to 500 µM. a) The percentage values of the control are given as Mean ± SD. The statistical significance of the deviations between the control and experimental groups was confirmed using the Welch t-test, where * at p<0.05, ** at p<0.01, *** at p<0.001, and **** at p<0.0001, n=5. b) A value of 50% of dead cells, designated as IC50, was selected as the reference point for cytotoxicity of the samples. The viability of human primary mesenchymal stem cells of the hMSc line decreased dose-dependently in the presence of the nanoconjugate during the entire 3 days of the experiment, reaching 10% of the control after 72 hours of coincubation with NDC-curcumin at a concentration of 500 µM (Figure 4a). It is worth noting that in the presence of the nanoconjugate, a higher level of cell viability was observed, as well as a lower percentage of dead cells, compared to curcumin alone (Figure 4b). This fact further confirms the hypothesis of the presence of excess colloidal curcumin as a cytotoxic component of the nanoconjugate. The results also indicate a low tolerance of hMSc cells to unbound curcumin. Figure 4 Cell viability (a) and dead cell percentage (b) of human primary mesenchymal stem cells of the hMSc line after 24, 48, and 72 hours of coincubation with NDC, curcumin and NDC-curcumin nanoconjugate in concentrations from 10 to 500 µM. a) The percentage values of the control are given as Mean ± SD. The statistical significance of the deviations between the control and experimental groups was confirmed using the Welch t-test, where * at p<0.05, ** at p<0.01, *** at p<0.001, and **** at p<0.0001, n=5. b) A value of 50% of dead cells, designated as IC50, was selected as the reference point for cytotoxicity of the samples. Scanning electron microscopy (c), distributions of hydrodynamic diameter (d) and zeta potential of the nanoconjugate (e). It has also been shown that the NDC-curcumin nanoconjugate exhibits dose-dependent cytotoxicity against human primary fibroblasts of the HF line at concentrations from 100 µM, similar to the above-described effect on HaCaT and hMSc cells (Figure 5). Thus, it can be confidently stated that during the formation of the nanoconjugate, NDC absorb curcumin on their surface, thereby reducing its potential cytotoxicity. Meanwhile, excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria. In addition, it is worth noting that fibroblasts are more resistant to the cytotoxic effects of excess curcumin than hMSc cells, but less resistant than HaCaT cells. Figure 5 Cell viability (a) and dead cell percentage (b) of human primary fibroblasts of the HF line after 24, 48, and 72 hours of coincubation with NDC, curcumin and NDC-curcumin nanoconjugate in concentrations from 10 to 500 µM. a) The percentage values of the control are given as Mean ± SD. The statistical significance of the deviations between the control and experimental groups was confirmed using the Welch t-test, where * at p<0.05, ** at p<0.01, *** at p<0.001, and **** at p<0.0001, n=5. b) A value of 50% of dead cells, designated as IC50, was selected as the reference point for cytotoxicity of the samples. We have shown a significant change in the optical characteristics, hydrodynamic size, and zeta potential of cerium dioxide nanoparticles upon their binding to curcumin. These changes indicate a direct interaction between NDC and curcumin, which may be due to the formation of coordination bonds between the Ce4+ ions present on the surface of the nanoparticles and the carbonyl groups of curcumin. Thus, the results of this work convincingly demonstrated the ability of cerium dioxide nanoparticles to form stable organo-inorganic structures with curcumin. This is largely consistent with the conclusions made earlier by other researchers [59, 60, 64–67] . At the same time, we found that excess curcumin, which is not bound to NDC, is capable of forming a polydisperse colloidal fraction with a particle size of about 50-100 nm. This fraction causes the dose-dependent cytotoxicity of the nanoconjugate in relation to human keratinocytes, mesenchymal stem cells and fibroblasts. Similar effects of decreased cell viability have previously been shown for free curcumin [68–71] . We suggest that the cytotoxicity of curcumin may be due to its incorporation into cell membrane structures due to its high hydrophobicity. It is important to note that at low concentrations, the nanoconjugate exhibits a high degree of biocompatibility, which corresponds to the available literature data on the biocompatibility of cerium dioxide nanoparticles [72–74] . NDC not only increases the bioavailability of curcumin, but also partially eliminates its potential cytotoxicity, which may be due to the antioxidant and cytoprotective properties of cerium dioxide nanoparticles [75, 76] . Thus, optimization of the synthesis scheme of curcumin nanoformulations with cerium dioxide nanoparticles, aimed at preventing the formation of excess free curcumin, is one of the key approaches to improve the safety of their biomedical applications. A promising area of further research is to determine the perfect ratio of NDC and curcumin, which ensures the most complete binding of these components. It is also of particular interest to study the bioactivity of the respective nanoformulation in vitro and in vivo . Conclusions Cerium dioxide nanoparticles represent an effective platform for binding and delivering curcumin, as they are able to form stable organo-inorganic nanoconjugates with it. However, such nanoformulations may contain excess curcumin, leading to their potential cytotoxicity. In turn, cerium dioxide nanoparticles, when binding curcumin, provide an increase in its biocompatibility. Thus, when developing curcumin nanoformulations, special attention should be paid to both the design of the synthesis scheme and the selection of their constituent components. It also seems advisable to conduct additional research to find the optimal ratio of the nanoconjugate components, in which their exhaustive binding would be observed. Moreover, the possible bioactivity of the corresponding nanoformulation is of particular interest. Experimental Reagents and synthesis Chemically pure curcumin, cerium ammonium nitrate ((NH 4 ) 2 Ce(NO 3 ) 6 ), polyvinylpyrrolidone (PVP) and 96% ethyl alcohol (Sigma-Alrdich, USA), as well as deionized water were used for the synthesis of NDC-curcumin nanoconjugate. MTT and Live/Dead assays were performed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide), Hoechst 33342 and propidium iodide (Lumiprobe, Russia) dyes. The synthesis of cerium dioxide nanoparticles was carried out according to the method previously developed by Shcherbakov and co-authors [77] . Next, the NDC-curcumin nanoconjugate was synthesized based on the technique presented earlier in the work by Zholobak et al. [67] . First, the synthesized NDC sol was mixed with an equal amount of PVP by weight in deionized water. The obtained NDC-PVP sol was dried in an ED 115 heating chamber (Binder, Germany) at 100°C. A curcumin-PVP solution with a mass ratio of 1 to 10 in 96% ethyl alcohol was prepared. The previously dried NDC-PVP sol was redispersed in 96% ethyl alcohol and the resulting colloidal solution was mixed with the previously prepared solution of curcumin-PVP with a molar ratio of NDC:curcumin equal to 10:1. The resulting NDC-curcumin nanoconjugate sol was dried in a heating chamber at 50 °C, then redispersed in deionized water. The individual samples of NDC and curcumin presented in the work were similarly stabilized using PVP. Physico-chemical properties The absorption spectra of the samples were analyzed using a Cary 5000 spectrophotometer (Agilent Technologies Inc., USA) in the wavelength range from 190 nm to 900 nm. The measurements were carried out in quartz cuvettes when diluting the samples in deionized water relative to the absorption of deionized water. The nanoscale fractions of the samples were determined by scanning electron microscopy using an NVision 40 electron microscope (Carl Zeiss, Germany) at an energy of 30 keV. The hydrodynamic size and zeta potential of the samples were measured by dynamic and electrophoretic light scattering in deionized water at 25°C using a BeNano 90 Zeta analyzer (Bettersize, China). Cell culture The experiments used cell lines of immortalized human keratinocytes (HaCaT), primary mesenchymal stem cells (hMSc) and primary fibroblasts (HF) provided from the cryobank of the Laboratory of Theranostics and Nuclear Medicine of the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences (http://nanomedlab.ru/). The cells were cultured using DMEM media with a high glucose content (for HaCaT) and DMEM/F12 (1:1) (for hMSc and HF) with the addition of 50 µg/mL penicillin, 50 µg/mL streptomycin, 2 mM L-glutamine and 10% fetal bovine serum (PanEco, Russia). Vials with a lid and a filter with a surface area of 25 and 75 cm 2 , as well as 96-well plates (SPL Life Sciences, Korea) were used for cell cultivation. The cells were cultured in a CO 2 incubator D180 (RWD Life Science, China) at a temperature of 37 °C, 5% CO 2 content and 95% humidity. The work with cell cultures was carried out in a laminar flow cabinet BMB-II-Laminar flow cabinet-1.2 (Neoteric, Russia). Cell viability The viability of cells after their coincubation with the studied samples was assessed using a routine MTT assay. The culture medium was replaced with an MTT solution in an appropriate serum-free medium at a concentration of 0.5 mg/mL. After 3 hours, the medium with MTT was replaced with pure DMSO, the plates were placed on a shaker for 10 minutes. Following this, the optical density of the solutions in the plate wells was measured at a wavelength of 570 nm using an INNO-S multimode plate reader (LTek, Korea). The measured optical density is directly related to the amount of formazane derivative recovered from MTT by cellular NADPH-dependent oxidoreductases. This value directly correlates with viability of cells. Optical density values were recalculated as a percentage of the control groups and presented as Mean. Deviations in the groups were indicated as a standard deviation (SD). The statistical significance of the deviations between the experimental and the control groups was confirmed using the Welch-corrected t-test at 0.01<p<0.05 (*), 0.001<p<0.01 (**), 0.0001<p<0.001 (***) and p<0.0001 (****) using GraphPad Prism software. Cell death The frequency of cell death after coincubation of cells with the studied samples was assessed using a routine Live/Dead assay. The culture medium was replaced with a solution of a mixture of fluorescent dyes Hoechst 33342 (binds to the DNA of all cells, Ex=350 nm, Em=460 nm) and propidium iodide (binds to the DNA of only dead cells, Ex= 535 nm, Em= 615 nm) in Hank’s Balanced Salt Solution (HBSS, PanEco, Russia). After 15 minutes, the cells were washed once with HBSS. Following this, cells were micrographed using a ZOE fluorescence microscope (Bio-Rad, USA). Using the ImageJ software, the total and dead cell numbers were counted, then their ratio was calculated. The IC50 value (50% of the total number of dead cells) was used as the reference point for cytotoxicity of the samples. Supporting Information The supporting information for this article is available on the WWW under https://doi.org/10.1002/cjoc.202400xxx. Acknowledgement This research was funded by the Russian Foundation, grant number №22-63-00082, https://rscf.ru/project/22-63-00082/. This research was performed using the equipment of the Joint Research centers in the Institute of Theoretical and Experimental Biophysics and the Kurnakov Institute of General and Inorganic Chemistry. References [1] Xu, X.-Y.; Meng, X.; Li, S.; Gan, R.-Y.; Li, Y.; Li, H.-B. Bioactivity, Health Benefits, and Related Molecular Mechanisms of Curcumin: Current Progress, Challenges, and Perspectives. 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DOI: 10.1002/cjoc.202400XXX Nanoceria (CeO 2 nanoparticles) forms a stable nanoconjugate with molecular curcumin, enhancing its biocompatibility. Excess curcumin forms a separate colloidal nanoscale fraction, which causes cytotoxicity of the nanoconjugate in relation to human healthy cells, including immortalized keratinocytes (HaCaT), primary mesenchymal stem cells (hMSc) and fibroblasts (HF). Information & Authors Information Version history V1 Version 1 10 June 2025 Peer review timeline Published Toxicology in Vitro Version of Record 1 Jan 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords curcumin cytotoxicity nanoceria nanoconjugate Authors Affiliations Chukavin N. N. 0000-0001-8431-4485 [email protected] FGBUN Institut teoreticeskoj i eksperimental'noj biofiziki Rossijskoj akademii nauk View all articles by this author Popov A. L. FGBUN Institut teoreticeskoj i eksperimental'noj biofiziki Rossijskoj akademii nauk View all articles by this author Viktoriia Anikina 0000-0002-5028-2064 FGBUN Institut teoreticeskoj i eksperimental'noj biofiziki Rossijskoj akademii nauk View all articles by this author Дарья Винник 0009-0004-8978-6923 FGBUN Institut teoreticeskoj i eksperimental'noj biofiziki Rossijskoj akademii nauk View all articles by this author Bokl B. A. FGBUN Institut teoreticeskoj i eksperimental'noj biofiziki Rossijskoj akademii nauk View all articles by this author Popova N. R. FGBUN Institut teoreticeskoj i eksperimental'noj biofiziki Rossijskoj akademii nauk View all articles by this author Metrics & Citations Metrics Article Usage 229 views 155 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Chukavin N. N., Popov A. L., Viktoriia Anikina, et al. Excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria. Authorea . 10 June 2025. 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