Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release
Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell mem...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/2014 |
| _version_ | 1797587779838803968 |
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| author | Fang Luo Ting Zhong Ying Chen Qianqian Guo Ling Tao Xiangchun Shen Yanhua Fan Xingjie Wu |
| author_facet | Fang Luo Ting Zhong Ying Chen Qianqian Guo Ling Tao Xiangchun Shen Yanhua Fan Xingjie Wu |
| author_sort | Fang Luo |
| collection | DOAJ |
| description | Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (<sup>1</sup>O<sub>2</sub>) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with <sup>1</sup>O<sub>2</sub> responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates <sup>1</sup>O<sub>2</sub>-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of <sup>1</sup>O<sub>2</sub>. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications. |
| first_indexed | 2024-03-11T00:43:44Z |
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| id | doaj.art-2f28c294f2b74763aed39742239975e8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:43:44Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2f28c294f2b74763aed39742239975e82023-11-18T20:56:59ZengMDPI AGPharmaceutics1999-49232023-07-01157201410.3390/pharmaceutics15072014Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug ReleaseFang Luo0Ting Zhong1Ying Chen2Qianqian Guo3Ling Tao4Xiangchun Shen5Yanhua Fan6Xingjie Wu7State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, ChinaDual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (<sup>1</sup>O<sub>2</sub>) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with <sup>1</sup>O<sub>2</sub> responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates <sup>1</sup>O<sub>2</sub>-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of <sup>1</sup>O<sub>2</sub>. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications.https://www.mdpi.com/1999-4923/15/7/2014synergistic targetingspecific treatmentdrug deliverycontrolled releasetumor chemotherapy |
| spellingShingle | Fang Luo Ting Zhong Ying Chen Qianqian Guo Ling Tao Xiangchun Shen Yanhua Fan Xingjie Wu Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release Pharmaceutics synergistic targeting specific treatment drug delivery controlled release tumor chemotherapy |
| title | Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release |
| title_full | Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release |
| title_fullStr | Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release |
| title_full_unstemmed | Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release |
| title_short | Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release |
| title_sort | dual ligand synergistic targeting anti tumor nanoplatforms with cascade responsive drug release |
| topic | synergistic targeting specific treatment drug delivery controlled release tumor chemotherapy |
| url | https://www.mdpi.com/1999-4923/15/7/2014 |
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