Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture
Good's buffers have been widely applied in cell/organ culture over the past half a century as biocompatible pH stabilizers. However, the emergence of severe adverse effects, such as cellular uptake, lysosomal autophagic activation, and visible light-induced cytotoxicity, raises serious question...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-06-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22005242 |
| _version_ | 1827267037480615936 |
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| author | Peiming Liu Jin Sun Wan Peng Yahui Gu Xiaoxue Ji Zhi Su Pingsheng Liu Jian Shen |
| author_facet | Peiming Liu Jin Sun Wan Peng Yahui Gu Xiaoxue Ji Zhi Su Pingsheng Liu Jian Shen |
| author_sort | Peiming Liu |
| collection | DOAJ |
| description | Good's buffers have been widely applied in cell/organ culture over the past half a century as biocompatible pH stabilizers. However, the emergence of severe adverse effects, such as cellular uptake, lysosomal autophagic activation, and visible light-induced cytotoxicity, raises serious questions over its biocompatibility while underlying mechanism was unclear. Here we report that riboflavin (RF, component of cell culture medium) generates 1O2, ·OH, and O2•- under visible light exposure during regular cell manipulation. These short half-life reactive oxygen species (ROS) react with tertiary amine groups of HEPES, producing 106.6 μM of H2O2. Orders of magnitude elevated half-life of ROS in the medium caused severe cytotoxicity and systematic disorder of normal cell functions. We have further designed and validated zwitterionic betaines as the new generation biocompatible organic pH buffers, which is able to completely avoid the adverse effects that found on HEPES and derivate Good's buffers. These findings may also open a new avenue for zwitterionic betaine based materials for biomedical applications. |
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| id | doaj.art-b21bd7f8a70d4f56957376d187e6d56a |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2025-03-22T04:27:22Z |
| publishDate | 2023-06-01 |
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| series | Bioactive Materials |
| spelling | doaj.art-b21bd7f8a70d4f56957376d187e6d56a2024-04-28T05:17:42ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-06-0124376386Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culturePeiming Liu0Jin Sun1Wan Peng2Yahui Gu3Xiaoxue Ji4Zhi Su5Pingsheng Liu6Jian Shen7Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, ChinaJiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, ChinaJiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, ChinaJiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, ChinaJiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, ChinaJiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, ChinaJiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, China; Corresponding author.Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, China; Jiangsu Engineering Research Center of Interfacial Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, 210093, China; Corresponding author. Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Jiangsu, 210023, China.Good's buffers have been widely applied in cell/organ culture over the past half a century as biocompatible pH stabilizers. However, the emergence of severe adverse effects, such as cellular uptake, lysosomal autophagic activation, and visible light-induced cytotoxicity, raises serious questions over its biocompatibility while underlying mechanism was unclear. Here we report that riboflavin (RF, component of cell culture medium) generates 1O2, ·OH, and O2•- under visible light exposure during regular cell manipulation. These short half-life reactive oxygen species (ROS) react with tertiary amine groups of HEPES, producing 106.6 μM of H2O2. Orders of magnitude elevated half-life of ROS in the medium caused severe cytotoxicity and systematic disorder of normal cell functions. We have further designed and validated zwitterionic betaines as the new generation biocompatible organic pH buffers, which is able to completely avoid the adverse effects that found on HEPES and derivate Good's buffers. These findings may also open a new avenue for zwitterionic betaine based materials for biomedical applications.http://www.sciencedirect.com/science/article/pii/S2452199X22005242Good's buffersZwitterionic betainesROS conversionCellular functionsBiocompatibility |
| spellingShingle | Peiming Liu Jin Sun Wan Peng Yahui Gu Xiaoxue Ji Zhi Su Pingsheng Liu Jian Shen Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture Bioactive Materials Good's buffers Zwitterionic betaines ROS conversion Cellular functions Biocompatibility |
| title | Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture |
| title_full | Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture |
| title_fullStr | Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture |
| title_full_unstemmed | Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture |
| title_short | Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture |
| title_sort | zwitterionic betaines over hepes as the new generation biocompatible ph buffers for cell culture |
| topic | Good's buffers Zwitterionic betaines ROS conversion Cellular functions Biocompatibility |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X22005242 |
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