Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing
Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/919 |
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| author | Alessia Marconi Giulia Giugliano Matteo Di Giosia Tainah Dorina Marforio Michele Trivini Eleonora Turrini Carmela Fimognari Francesco Zerbetto Edoardo Jun Mattioli Matteo Calvaresi |
| author_facet | Alessia Marconi Giulia Giugliano Matteo Di Giosia Tainah Dorina Marforio Michele Trivini Eleonora Turrini Carmela Fimognari Francesco Zerbetto Edoardo Jun Mattioli Matteo Calvaresi |
| author_sort | Alessia Marconi |
| collection | DOAJ |
| description | Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the main limitations because they cause poor stability in physiological environments, dark toxicity, and ultimately reduce the generation of reactive oxygen species (ROS). Applying a reverse docking approach, here, we identified a number of blood transport proteins able to bind and disperse monomolecularly mTHPC, namely apohemoglobin, apomyoglobin, hemopexin, and afamin. We validated the computational results synthesizing the mTHPC-apomyoglobin complex (mTHPC@apoMb) and demonstrated that the protein monodisperses mTHPC in a physiological environment. The mTHPC@apoMb complex preserves the imaging properties of the molecule and improves its ability to produce ROS via both type I and type II mechanisms. The effectiveness of photodynamic treatment using the mTHPC@apoMb complex was then demonstrated in vitro. Blood transport proteins can be used as molecular “Trojan horses” in cancer cells by conferring mTHPC (i) water solubility, (ii) monodispersity, and (iii) biocompatibility, ultimately bypassing the current limitations of mTHPC. |
| first_indexed | 2024-03-11T06:02:49Z |
| format | Article |
| id | doaj.art-facad439afc64694bdb1741ddd4791ac |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:02:49Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-facad439afc64694bdb1741ddd4791ac2023-11-17T13:16:15ZengMDPI AGPharmaceutics1999-49232023-03-0115391910.3390/pharmaceutics15030919Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT TestingAlessia Marconi0Giulia Giugliano1Matteo Di Giosia2Tainah Dorina Marforio3Michele Trivini4Eleonora Turrini5Carmela Fimognari6Francesco Zerbetto7Edoardo Jun Mattioli8Matteo Calvaresi9Dipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Scienze per la Qualità della Vita, Alma Mater Studiorum—Università di Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDipartimento di Scienze per la Qualità della Vita, Alma Mater Studiorum—Università di Bologna, Corso d’Augusto 237, 47921 Rimini, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum—Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyTemoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the main limitations because they cause poor stability in physiological environments, dark toxicity, and ultimately reduce the generation of reactive oxygen species (ROS). Applying a reverse docking approach, here, we identified a number of blood transport proteins able to bind and disperse monomolecularly mTHPC, namely apohemoglobin, apomyoglobin, hemopexin, and afamin. We validated the computational results synthesizing the mTHPC-apomyoglobin complex (mTHPC@apoMb) and demonstrated that the protein monodisperses mTHPC in a physiological environment. The mTHPC@apoMb complex preserves the imaging properties of the molecule and improves its ability to produce ROS via both type I and type II mechanisms. The effectiveness of photodynamic treatment using the mTHPC@apoMb complex was then demonstrated in vitro. Blood transport proteins can be used as molecular “Trojan horses” in cancer cells by conferring mTHPC (i) water solubility, (ii) monodispersity, and (iii) biocompatibility, ultimately bypassing the current limitations of mTHPC.https://www.mdpi.com/1999-4923/15/3/919dockingvirtual screeningMD simulationsMM-GBSAtemoporfin (mTHPC)apomyoglobin |
| spellingShingle | Alessia Marconi Giulia Giugliano Matteo Di Giosia Tainah Dorina Marforio Michele Trivini Eleonora Turrini Carmela Fimognari Francesco Zerbetto Edoardo Jun Mattioli Matteo Calvaresi Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing Pharmaceutics docking virtual screening MD simulations MM-GBSA temoporfin (mTHPC) apomyoglobin |
| title | Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing |
| title_full | Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing |
| title_fullStr | Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing |
| title_full_unstemmed | Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing |
| title_short | Identification of Blood Transport Proteins to Carry Temoporfin: A Domino Approach from Virtual Screening to Synthesis and In Vitro PDT Testing |
| title_sort | identification of blood transport proteins to carry temoporfin a domino approach from virtual screening to synthesis and in vitro pdt testing |
| topic | docking virtual screening MD simulations MM-GBSA temoporfin (mTHPC) apomyoglobin |
| url | https://www.mdpi.com/1999-4923/15/3/919 |
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