Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma
A novel treatment strategy by co-targeting c-Myc and tumor stroma was explored in vemurafenib-resistant melanoma. BRD4 proteolysis targeting chimera (ARV-825) and nintedanib co-loaded PEGylated nanoliposomes (ARNIPL) were developed to incorporate a synergistic cytotoxic ratio. Both the molecules hav...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/7/1005 |
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| author | Yige Fu Aishwarya Saraswat Zenghui Wei Manas Yogendra Agrawal Vikas V. Dukhande Sandra E. Reznik Ketan Patel |
| author_facet | Yige Fu Aishwarya Saraswat Zenghui Wei Manas Yogendra Agrawal Vikas V. Dukhande Sandra E. Reznik Ketan Patel |
| author_sort | Yige Fu |
| collection | DOAJ |
| description | A novel treatment strategy by co-targeting c-Myc and tumor stroma was explored in vemurafenib-resistant melanoma. BRD4 proteolysis targeting chimera (ARV-825) and nintedanib co-loaded PEGylated nanoliposomes (ARNIPL) were developed to incorporate a synergistic cytotoxic ratio. Both the molecules have extremely poor aqueous solubility. A modified hydration method with citric acid was used to improve the loading of both the molecules in liposomes. ARNIPL with mean particle size 111.1 ± 6.55 nm exhibited more than 90% encapsulation efficiency for both the drugs and was found to be physically stable for a month at 4 °C. Both the molecules and ARNIPL showed significantly higher cytotoxicity, apoptosis and down-regulation of target proteins BRD4 and c-Myc in vemurafenib-resistant cell line (A375R). Vasculogenic mimicry and clonogenic potential of A375R were significantly inhibited by ARNIPL. Tumor growth inhibition in 3D spheroids with reduction of TGF-β1 was observed with ARNIPL treatment. Therefore, ARNIPL could be a promising therapeutic approach for the treatment of vemurafenib-resistant melanoma. |
| first_indexed | 2024-03-10T09:29:00Z |
| format | Article |
| id | doaj.art-c3edc51cc9e54d0a8d8965a4cd2cc24c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T09:29:00Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c3edc51cc9e54d0a8d8965a4cd2cc24c2023-11-22T04:40:35ZengMDPI AGPharmaceutics1999-49232021-07-01137100510.3390/pharmaceutics13071005Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant MelanomaYige Fu0Aishwarya Saraswat1Zenghui Wei2Manas Yogendra Agrawal3Vikas V. Dukhande4Sandra E. Reznik5Ketan Patel6College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USAA novel treatment strategy by co-targeting c-Myc and tumor stroma was explored in vemurafenib-resistant melanoma. BRD4 proteolysis targeting chimera (ARV-825) and nintedanib co-loaded PEGylated nanoliposomes (ARNIPL) were developed to incorporate a synergistic cytotoxic ratio. Both the molecules have extremely poor aqueous solubility. A modified hydration method with citric acid was used to improve the loading of both the molecules in liposomes. ARNIPL with mean particle size 111.1 ± 6.55 nm exhibited more than 90% encapsulation efficiency for both the drugs and was found to be physically stable for a month at 4 °C. Both the molecules and ARNIPL showed significantly higher cytotoxicity, apoptosis and down-regulation of target proteins BRD4 and c-Myc in vemurafenib-resistant cell line (A375R). Vasculogenic mimicry and clonogenic potential of A375R were significantly inhibited by ARNIPL. Tumor growth inhibition in 3D spheroids with reduction of TGF-β1 was observed with ARNIPL treatment. Therefore, ARNIPL could be a promising therapeutic approach for the treatment of vemurafenib-resistant melanoma.https://www.mdpi.com/1999-4923/13/7/1005ARV-825proteolysis targeting chimeranintedanibvemurafenib-resistant melanomaPEGylated nanoliposomessynergistic interaction |
| spellingShingle | Yige Fu Aishwarya Saraswat Zenghui Wei Manas Yogendra Agrawal Vikas V. Dukhande Sandra E. Reznik Ketan Patel Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma Pharmaceutics ARV-825 proteolysis targeting chimera nintedanib vemurafenib-resistant melanoma PEGylated nanoliposomes synergistic interaction |
| title | Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma |
| title_full | Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma |
| title_fullStr | Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma |
| title_full_unstemmed | Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma |
| title_short | Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma |
| title_sort | development of dual arv 825 and nintedanib loaded pegylated nano liposomes for synergistic efficacy in vemurafnib resistant melanoma |
| topic | ARV-825 proteolysis targeting chimera nintedanib vemurafenib-resistant melanoma PEGylated nanoliposomes synergistic interaction |
| url | https://www.mdpi.com/1999-4923/13/7/1005 |
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