Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells
Objective: The objective of this study was to examine the preparation process of DSPE-PEG-C60/NCTD micelles and assess the impact of fullerenol (C60)-modified micelles on the nephrotoxicity and antitumor activity of NCTD. Method: The micelles containing NCTD were prepared using the ultrasonic method...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/22/7609 |
| _version_ | 1827639162236305408 |
|---|---|
| author | Zhongpeng Ding Beihua Xu Huimin Zhang Zhenyu Wang Luying Sun Mengjie Tang Meihong Ding Ting Zhang Senlin Shi |
| author_facet | Zhongpeng Ding Beihua Xu Huimin Zhang Zhenyu Wang Luying Sun Mengjie Tang Meihong Ding Ting Zhang Senlin Shi |
| author_sort | Zhongpeng Ding |
| collection | DOAJ |
| description | Objective: The objective of this study was to examine the preparation process of DSPE-PEG-C60/NCTD micelles and assess the impact of fullerenol (C60)-modified micelles on the nephrotoxicity and antitumor activity of NCTD. Method: The micelles containing NCTD were prepared using the ultrasonic method and subsequently optimized and characterized. The cytotoxicity of micelles loaded with NCTD was assessed using the CCK-8 method on human hepatoma cell lines HepG2 and BEL-7402, as well as normal cell lines HK-2 and L02. Acridine orange/ethidium bromide (AO/EB) double staining and flow cytometry were employed to assess the impact of NCTD-loaded micelles on the apoptosis of the HK-2 cells and the HepG2 cells. Additionally, JC-1 fluorescence was utilized to quantify the alterations in mitochondrial membrane potential. The generation of reactive oxygen species (ROS) following micelle treatment was determined through 2′,7′-dichlorofluorescein diacetate (DCFDA) staining. Results: The particle size distribution of the DSPE-PEG-C60/NCTD micelles was determined to be 91.57 nm (PDI = 0.231). The zeta potential of the micelles was found to be −13.8 mV. The encapsulation efficiency was measured to be 91.9%. The in vitro release behavior of the micelles followed the Higuchi equation. Cellular experiments demonstrated a notable decrease in the toxicity of the C60-modified micelles against the HK-2 cells, accompanied by an augmented inhibitory effect on cancer cells. Compared to the free NCTD group, the DSPE-PEG-C60 micelles exhibited a decreased apoptosis rate (12%) for the HK-2 cell line, lower than the apoptosis rate observed in the NCTD group (36%) at an NCTD concentration of 75 μM. The rate of apoptosis in the HepG2 cells exhibited a significant increase (49%), surpassing the apoptosis rate observed in the NCTD group (24%) at a concentration of 150 μM NCTD. The HK-2 cells exhibited a reduction in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM) upon exposure to C60-modified micelles compared to the NCTD group. Conclusions: The DSPE-PEG-C60/NCTD micelles, as prepared in this study, demonstrated the ability to decrease cytotoxicity and ROS levels in normal renal cells (HK-2) in vitro. Additionally, these micelles showed an enhanced antitumor activity against human hepatocellular carcinoma cells (HepG2, BEL-7402). |
| first_indexed | 2024-03-09T16:34:46Z |
| format | Article |
| id | doaj.art-e6fed45979764541817f907ce8c9201a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:34:46Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e6fed45979764541817f907ce8c9201a2023-11-24T14:58:25ZengMDPI AGMolecules1420-30492023-11-012822760910.3390/molecules28227609Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma CellsZhongpeng Ding0Beihua Xu1Huimin Zhang2Zhenyu Wang3Luying Sun4Mengjie Tang5Meihong Ding6Ting Zhang7Senlin Shi8College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, ChinaObjective: The objective of this study was to examine the preparation process of DSPE-PEG-C60/NCTD micelles and assess the impact of fullerenol (C60)-modified micelles on the nephrotoxicity and antitumor activity of NCTD. Method: The micelles containing NCTD were prepared using the ultrasonic method and subsequently optimized and characterized. The cytotoxicity of micelles loaded with NCTD was assessed using the CCK-8 method on human hepatoma cell lines HepG2 and BEL-7402, as well as normal cell lines HK-2 and L02. Acridine orange/ethidium bromide (AO/EB) double staining and flow cytometry were employed to assess the impact of NCTD-loaded micelles on the apoptosis of the HK-2 cells and the HepG2 cells. Additionally, JC-1 fluorescence was utilized to quantify the alterations in mitochondrial membrane potential. The generation of reactive oxygen species (ROS) following micelle treatment was determined through 2′,7′-dichlorofluorescein diacetate (DCFDA) staining. Results: The particle size distribution of the DSPE-PEG-C60/NCTD micelles was determined to be 91.57 nm (PDI = 0.231). The zeta potential of the micelles was found to be −13.8 mV. The encapsulation efficiency was measured to be 91.9%. The in vitro release behavior of the micelles followed the Higuchi equation. Cellular experiments demonstrated a notable decrease in the toxicity of the C60-modified micelles against the HK-2 cells, accompanied by an augmented inhibitory effect on cancer cells. Compared to the free NCTD group, the DSPE-PEG-C60 micelles exhibited a decreased apoptosis rate (12%) for the HK-2 cell line, lower than the apoptosis rate observed in the NCTD group (36%) at an NCTD concentration of 75 μM. The rate of apoptosis in the HepG2 cells exhibited a significant increase (49%), surpassing the apoptosis rate observed in the NCTD group (24%) at a concentration of 150 μM NCTD. The HK-2 cells exhibited a reduction in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM) upon exposure to C60-modified micelles compared to the NCTD group. Conclusions: The DSPE-PEG-C60/NCTD micelles, as prepared in this study, demonstrated the ability to decrease cytotoxicity and ROS levels in normal renal cells (HK-2) in vitro. Additionally, these micelles showed an enhanced antitumor activity against human hepatocellular carcinoma cells (HepG2, BEL-7402).https://www.mdpi.com/1420-3049/28/22/7609norcantharidinattenuateC60nanomicelleshepatic carcinoma |
| spellingShingle | Zhongpeng Ding Beihua Xu Huimin Zhang Zhenyu Wang Luying Sun Mengjie Tang Meihong Ding Ting Zhang Senlin Shi Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells Molecules norcantharidin attenuate C60 nanomicelles hepatic carcinoma |
| title | Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells |
| title_full | Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells |
| title_fullStr | Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells |
| title_full_unstemmed | Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells |
| title_short | Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells |
| title_sort | norcantharidin encapsulated c60 modified nanomicelles a potential approach to mitigate cytotoxicity in renal cells and simultaneously enhance anti tumor activity in hepatocellular carcinoma cells |
| topic | norcantharidin attenuate C60 nanomicelles hepatic carcinoma |
| url | https://www.mdpi.com/1420-3049/28/22/7609 |
| work_keys_str_mv | AT zhongpengding norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT beihuaxu norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT huiminzhang norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT zhenyuwang norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT luyingsun norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT mengjietang norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT meihongding norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT tingzhang norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells AT senlinshi norcantharidinencapsulatedc60modifiednanomicellesapotentialapproachtomitigatecytotoxicityinrenalcellsandsimultaneouslyenhanceantitumoractivityinhepatocellularcarcinomacells |