Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes
Encapsulation of Doxorubicin (Dox), a potent cytotoxic agent and immunogenic cell death inducer, in pegylated (Stealth) liposomes, is well known to have major pharmacologic advantages over treatment with free Dox. Reformulation of alendronate (Ald), a potent amino-bisphosphonate, by encapsulation in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/11/2606 |
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| author | Alberto Gabizon Hilary Shmeeda Benjamin Draper Ana Parente-Pereira John Maher Amaia Carrascal-Miniño Rafael T. M. de Rosales Ninh M. La-Beck |
| author_facet | Alberto Gabizon Hilary Shmeeda Benjamin Draper Ana Parente-Pereira John Maher Amaia Carrascal-Miniño Rafael T. M. de Rosales Ninh M. La-Beck |
| author_sort | Alberto Gabizon |
| collection | DOAJ |
| description | Encapsulation of Doxorubicin (Dox), a potent cytotoxic agent and immunogenic cell death inducer, in pegylated (Stealth) liposomes, is well known to have major pharmacologic advantages over treatment with free Dox. Reformulation of alendronate (Ald), a potent amino-bisphosphonate, by encapsulation in pegylated liposomes, results in significant immune modulatory effects through interaction with tumor-associated macrophages and activation of a subset of gamma-delta T lymphocytes. We present here recent findings of our research work with a formulation of Dox and Ald co-encapsulated in pegylated liposomes (PLAD) and discuss its pharmacological properties vis-à-vis free Dox and the current clinical formulation of pegylated liposomal Dox. PLAD is a robust formulation with high and reproducible remote loading of Dox and high stability in plasma. Results of biodistribution studies, imaging with radionuclide-labeled liposomes, and therapeutic studies as a single agent and in combination with immune checkpoint inhibitors or gamma-delta T lymphocytes suggest that PLAD is a unique product with distinct tumor microenvironmental interactions and distinct pharmacologic properties when compared with free Dox and the clinical formulation of pegylated liposomal Dox. These results underscore the potential added value of PLAD for chemo-immunotherapy of cancer and the relevance of the co-encapsulation approach in nanomedicine. |
| first_indexed | 2024-03-09T16:31:51Z |
| format | Article |
| id | doaj.art-e363bd6344c14088aaee1897c4370011 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T16:31:51Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e363bd6344c14088aaee1897c43700112023-11-24T15:01:05ZengMDPI AGPharmaceutics1999-49232023-11-011511260610.3390/pharmaceutics15112606Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated LiposomesAlberto Gabizon0Hilary Shmeeda1Benjamin Draper2Ana Parente-Pereira3John Maher4Amaia Carrascal-Miniño5Rafael T. M. de Rosales6Ninh M. La-Beck7Nano-Oncology Research Center, Oncology Institute, Shaare Zedek Medical Center, Jerusalem 9103102, IsraelNano-Oncology Research Center, Oncology Institute, Shaare Zedek Medical Center, Jerusalem 9103102, IsraelKing’s College London, School of Cancer and Pharmaceutical Sciences, Guy’s Cancer Centre, Great Maze Pond, London SE1 9RT, UKKing’s College London, School of Cancer and Pharmaceutical Sciences, Guy’s Cancer Centre, Great Maze Pond, London SE1 9RT, UKKing’s College London, School of Cancer and Pharmaceutical Sciences, Guy’s Cancer Centre, Great Maze Pond, London SE1 9RT, UKKing’s College London, School of Biomedical Engineering & Imaging Sciences, St. Thomas’ Hospital, London SE1 7EH, UKKing’s College London, School of Biomedical Engineering & Imaging Sciences, St. Thomas’ Hospital, London SE1 7EH, UKDepartment of Immunotherapeutics and Biotechnology, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX 79601, USAEncapsulation of Doxorubicin (Dox), a potent cytotoxic agent and immunogenic cell death inducer, in pegylated (Stealth) liposomes, is well known to have major pharmacologic advantages over treatment with free Dox. Reformulation of alendronate (Ald), a potent amino-bisphosphonate, by encapsulation in pegylated liposomes, results in significant immune modulatory effects through interaction with tumor-associated macrophages and activation of a subset of gamma-delta T lymphocytes. We present here recent findings of our research work with a formulation of Dox and Ald co-encapsulated in pegylated liposomes (PLAD) and discuss its pharmacological properties vis-à-vis free Dox and the current clinical formulation of pegylated liposomal Dox. PLAD is a robust formulation with high and reproducible remote loading of Dox and high stability in plasma. Results of biodistribution studies, imaging with radionuclide-labeled liposomes, and therapeutic studies as a single agent and in combination with immune checkpoint inhibitors or gamma-delta T lymphocytes suggest that PLAD is a unique product with distinct tumor microenvironmental interactions and distinct pharmacologic properties when compared with free Dox and the clinical formulation of pegylated liposomal Dox. These results underscore the potential added value of PLAD for chemo-immunotherapy of cancer and the relevance of the co-encapsulation approach in nanomedicine.https://www.mdpi.com/1999-4923/15/11/2606liposomedoxorubicinalendronateco-encapsulationchemotherapyimmunotherapy |
| spellingShingle | Alberto Gabizon Hilary Shmeeda Benjamin Draper Ana Parente-Pereira John Maher Amaia Carrascal-Miniño Rafael T. M. de Rosales Ninh M. La-Beck Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes Pharmaceutics liposome doxorubicin alendronate co-encapsulation chemotherapy immunotherapy |
| title | Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes |
| title_full | Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes |
| title_fullStr | Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes |
| title_full_unstemmed | Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes |
| title_short | Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes |
| title_sort | harnessing nanomedicine to potentiate the chemo immunotherapeutic effects of doxorubicin and alendronate co encapsulated in pegylated liposomes |
| topic | liposome doxorubicin alendronate co-encapsulation chemotherapy immunotherapy |
| url | https://www.mdpi.com/1999-4923/15/11/2606 |
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