Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy
Owing to its pH-sensitive property and chelating Cu<sup>2+</sup> effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/9/1765 |
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| author | Bo Yu Yiping Shen Xuejie Zhang Lijuan Ding Zheng Meng Xiaotong Wang Meihua Han Yifei Guo Xiangtao Wang |
| author_facet | Bo Yu Yiping Shen Xuejie Zhang Lijuan Ding Zheng Meng Xiaotong Wang Meihua Han Yifei Guo Xiangtao Wang |
| author_sort | Bo Yu |
| collection | DOAJ |
| description | Owing to its pH-sensitive property and chelating Cu<sup>2+</sup> effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC<sub>50</sub> value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application. |
| first_indexed | 2024-03-09T22:51:12Z |
| format | Article |
| id | doaj.art-4405587741234de592c2c98875b30eda |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:51:12Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4405587741234de592c2c98875b30eda2023-11-23T18:20:05ZengMDPI AGPharmaceutics1999-49232022-08-01149176510.3390/pharmaceutics14091765Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor TherapyBo Yu0Yiping Shen1Xuejie Zhang2Lijuan Ding3Zheng Meng4Xiaotong Wang5Meihua Han6Yifei Guo7Xiangtao Wang8Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, ChinaOwing to its pH-sensitive property and chelating Cu<sup>2+</sup> effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC<sub>50</sub> value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application.https://www.mdpi.com/1999-4923/14/9/1765poly(methacrylate citric acid)doxorubicinpH sensitivechelating Cu<sup>2+</sup> effect |
| spellingShingle | Bo Yu Yiping Shen Xuejie Zhang Lijuan Ding Zheng Meng Xiaotong Wang Meihua Han Yifei Guo Xiangtao Wang Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy Pharmaceutics poly(methacrylate citric acid) doxorubicin pH sensitive chelating Cu<sup>2+</sup> effect |
| title | Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy |
| title_full | Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy |
| title_fullStr | Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy |
| title_full_unstemmed | Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy |
| title_short | Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy |
| title_sort | poly methacrylate citric acid as a dual functional carrier for tumor therapy |
| topic | poly(methacrylate citric acid) doxorubicin pH sensitive chelating Cu<sup>2+</sup> effect |
| url | https://www.mdpi.com/1999-4923/14/9/1765 |
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