Acute and Subacute Toxicity Study of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes

Gao, Wenchao; Zhang, Junfeng; Xue, Qianghua; Yin, Xia; Yin, Xi‐Jun; Li, Chenchen; Wang, Yanli

doi:10.1021/acs.molpharmaceut.0c00380

Cited by 8 publications

(4 citation statements)

References 45 publications

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“…[ 14 ] With small size, non‐toxic, good biocompatibility, and fast metabolic rate, these CBNs have great potential to become excellent nanodrug carriers. [ 14b,15 ] We coated CBNs with Pluronic F127 and combined it with DOX to successfully prepare the CBNs‐Pluronic F127‐DOX (CPD) nanodrug delivery system. As result, the DOX targeting rate of CPD in tumor nucleus was as high as 36.78%, and the %ID/g in tumor tissue as high as 30.09%, resulting in tumor growth inhibition rate as high as 79.42 ± 2.83%, and greatly reduced the systemic side effects of DOX.…”

Section: Introductionmentioning

confidence: 99%

An Efficient Carbon‐Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway

Zhang

Xue

et al. 2021

Small Methods

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such as poor water solubility, [2] low bioavailability, rapid blood clearance, and multidrug resistance. [3] In order to solve these problems, drug delivery systems based on nanocarriers have been extensively developed, which not only increase the drug loading capacity and blood time of the target drug, but also reduce the potential systemic toxicity of the loaded drug. [4] So far, traditional nanocarriers are generally composed of inorganic materials such as carbon-based nanomaterials (CBNs), [5] magnetic particles, [6] silica, [7] gold-based nanomaterials, [8] and organic molecules such as polymer NPs, [9] liposomes, [10] micelles, [11] etc. Among them, CBNs have the characteristics of biocompatibility, low toxicity, high water-solubility, and potential to conjugate various molecules, they have been widely used in drug delivery, cancer diagnosis and therapy, and other fields, and are considered as an excellent nanocarrier. [12] It has been reported that CBNs loaded with DOX can be used to target tumor cell nucleus, but in order to improve the drug targeting rate, it is usually necessary to modify active targeting ligands, such as antibodies, folic acid, and peptides (RGD and nuclear targeting peptides), etc. However, these active targeting ligands have potential drawbacks while improving drug targeting, such as the high cost of antibodies and low tumor penetration due to their large size, the low stability of aptamers due to the nucleases in blood plasma, and the low circulating half-life of The emergence of nanocarriers solves the problems of antitumor drugs such as non-targeting, huge side effects, etc., and has been widely used in tumor therapy. Some kinds of antitumor drugs such as doxorubicin (DOX) mainly act on the nucleic acid causing DNA damage, interfering with transcription, and thereby disrupting or blocking the process of cancer cell replication. Herein, a new nanodrug delivery system, the carbon-based nanomaterials (CBNs)-Pluronic F127-DOX (CPD), is designed by using CBNs as a nanocarrier for DOX. As a result, the tumor growth inhibition rate of CPD group is as high as 79.42 ± 2.83%, and greatly reduces the side effects. The targeting rate of the CPD group of DOX in the tumor nucleus is 36.78%, and the %ID/g in tumor tissue is 30.09%. The CPD regulates the expression levels of Caspase-3, p53, and Bcl-2 genes by increasing intracellular reactive oxygen species (ROS) levels and reducing mitochondrial membrane potential, which indicates that mitochondrial-mediated pathways are involved in apoptosis. The CPD nanodrug delivery system increases the effective accumulation of DOX in tumor cell nuclei and tumor tissues, and generates massive ROS, thereby inhibiting tumor growth in vivo, representing a promising agent for anticancer applications.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smtd.202100539.

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Section: Introductionmentioning

confidence: 99%

An Efficient Carbon‐Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway

Zhang

Xue

et al. 2021

Small Methods

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“…Few studies focus on GFNs nuclear detecting techniques. In the biological imaging field, most research pays attention to safe application of fluorescent GFNs nuclear images rather than assessing genotoxicity of GFNs from an environmental toxicology point of view [135][136][137]. It is necessary to further optimize and develop detection techniques of GFNs in cells and organism tissues for a better understanding of genotoxicity.…”

Section: Detection Of Gfns In Cells and Organism Tissuesmentioning

confidence: 99%

Direct and Indirect Genotoxicity of Graphene Family Nanomaterials on DNA—A Review

Zhou

Ouyang

2021

Nanomaterials

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Graphene family nanomaterials (GFNs), including graphene, graphene oxide (GO), reduced graphene oxide (rGO), and graphene quantum dots (GQDs), have manifold potential applications, leading to the possibility of their release into environments and the exposure to humans and other organisms. However, the genotoxicity of GFNs on DNA remains largely unknown. In this review, we highlight the interactions between DNA and GFNs and summarize the mechanisms of genotoxicity induced by GFNs. Generally, the genotoxicity can be sub-classified into direct genotoxicity and indirect genotoxicity. The direct genotoxicity (e.g., direct physical nucleus and DNA damage) and indirect genotoxicity mechanisms (e.g., physical destruction, oxidative stress, epigenetic toxicity, and DNA replication) of GFNs were summarized in the manuscript, respectively. Moreover, the influences factors, such as physicochemical properties, exposure dose, and time, on the genotoxicity of GFNs are also briefly discussed. Given the important role of genotoxicity in GFNs exposure risk assessment, future research should be conducted on the following: (1) developing reliable testing methods; (2) elucidating the response mechanisms associated with genotoxicity in depth; and (3) enriching the evaluation database regarding the type of GFNs, applied dosages, and exposure times.

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“…In previous studies, we evaluated cytotoxicity in vitro and acute and subacute toxicity in vivo. 37,39 The results indicated that exposure to GTTNs showed little cytotoxicity, acute and subacute toxicity by CCK-8, behavior, organ coefficients, body weight, histological examinations, and biochemistry. It is well known that the male reproductive system is more susceptible to many exogenous materials compared with other organ systems.…”

Section: ■ Introductionmentioning

confidence: 99%

“…These remarkable properties suggest that GTTNs have broad potential in tumor diagnosis and therapy. In previous studies, we evaluated cytotoxicity in vitro and acute and subacute toxicity in vivo . , The results indicated that exposure to GTTNs showed little cytotoxicity, acute and subacute toxicity by CCK-8, behavior, organ coefficients, body weight, histological examinations, and biochemistry. It is well known that the male reproductive system is more susceptible to many exogenous materials compared with other organ systems. , However, the toxicity of GTTNs to the male reproductive system and offspring development has not been investigated yet.…”

Section: Introductionmentioning

confidence: 99%

Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health

et al. 2023

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A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.

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Acute and Subacute Toxicity Study of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes

Cited by 8 publications

References 45 publications

An Efficient Carbon‐Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway

An Efficient Carbon‐Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway

Direct and Indirect Genotoxicity of Graphene Family Nanomaterials on DNA—A Review

Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health

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