Carbon dots conjugated to SN38 for improved colorectal anticancer therapy
Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically converted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to impro...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006422000849 |
| _version_ | 1811235365822922752 |
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| author | Deborah Mattinzoli Michele Cacioppo Masami Ikehata Silvia Armelloni Carlo Maria Alfieri Giuseppe Castellano Mario Barilani Francesca Arcudi Piergiorgio Messa Maurizio Prato |
| author_facet | Deborah Mattinzoli Michele Cacioppo Masami Ikehata Silvia Armelloni Carlo Maria Alfieri Giuseppe Castellano Mario Barilani Francesca Arcudi Piergiorgio Messa Maurizio Prato |
| author_sort | Deborah Mattinzoli |
| collection | DOAJ |
| description | Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically converted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to improve their solubility, efficacy, and selectivity. Carbon dots (CDs) have garnered interest for their small sizes (<10 nm), low toxicity, high water solubility, and bright fluorescence. This paper describes the use of CDs to improve drug vehiculation, stability, and chemotherapeutic efficiency of SN38 through a direct intracellular uptake in CRC. The covalent conjugation of SN38 to CDs via a carbamate bond provides a CD-SN38 hybrid material for slow, sustained, and pH-responsive drug release. CD-SN38 successfully penetrates the CRC cells with a release in the nucleus affecting first the cell cycle and then the cytoskeleton. Moreover, CD-SN38 leads to a deregulation of the extracellular matrix (ECM), one of the major components of the cancer niche considered a possible target therapy for reducing the cancer progression. This work shows the combined therapeutic and imaging potential of CD-based hybrid materials for the treatment of CRC. Future efforts for targeted therapy of chronic diseases characterized by altered ECM deposition, such as chronic kidney disease and chronic allograft nephropathy in kidney transplant patients are envisaged. |
| first_indexed | 2024-04-12T11:49:37Z |
| format | Article |
| id | doaj.art-9b61cc2e8afe400daaf7ee361eb06915 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-12T11:49:37Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-9b61cc2e8afe400daaf7ee361eb069152022-12-22T03:34:13ZengElsevierMaterials Today Bio2590-00642022-12-0116100286Carbon dots conjugated to SN38 for improved colorectal anticancer therapyDeborah Mattinzoli0Michele Cacioppo1Masami Ikehata2Silvia Armelloni3Carlo Maria Alfieri4Giuseppe Castellano5Mario Barilani6Francesca Arcudi7Piergiorgio Messa8Maurizio Prato9Renal Research Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9, Milan, 20122, Italy; Corresponding author.Department of Chemical and Pharmaceutical Sciences, INSTM UdR Trieste, University of Trieste, Via Licio Giorgieri 1, Trieste, 34127, Italy; Center for Cooperative Research in Biomaterials (CIC BiomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramón 182, Donostia-San Sebastián, 20014, SpainRenal Research Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9, Milan, 20122, ItalyRenal Research Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9, Milan, 20122, ItalyUnit of Nephrology, Dialysis and Renal Transplant Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Della Commenda 15, Milan, 20122, Italy; University of Study of Milan, Via Festa Del Perdono 7, 20122, Milan, Italy; Corresponding author. University of Study of Milan, via Festa Del Perdono 7, 20122, Milan, Italy.Unit of Nephrology, Dialysis and Renal Transplant Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Della Commenda 15, Milan, 20122, Italy; University of Study of Milan, Via Festa Del Perdono 7, 20122, Milan, ItalyEPIGET LAB, Department of Clinical Sciences and Community Health, University of Milan, Milan, 20122, Italy; Department of Transfusion Medicine and Hematology, Cell Factory, Regenerative Medicine Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, 20122, ItalyDepartment of Chemical and Pharmaceutical Sciences, INSTM UdR Trieste, University of Trieste, Via Licio Giorgieri 1, Trieste, 34127, Italy; Corresponding author.Unit of Nephrology, Dialysis and Renal Transplant Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Della Commenda 15, Milan, 20122, Italy; University of Study of Milan, Via Festa Del Perdono 7, 20122, Milan, ItalyDepartment of Chemical and Pharmaceutical Sciences, INSTM UdR Trieste, University of Trieste, Via Licio Giorgieri 1, Trieste, 34127, Italy; Center for Cooperative Research in Biomaterials (CIC BiomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramón 182, Donostia-San Sebastián, 20014, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, 48013, Spain; Corresponding author. Department of Chemical and Pharmaceutical Sciences, INSTM UdR Trieste, University of Trieste, via Licio Giorgieri 1, Trieste, 34127, Italy.Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically converted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to improve their solubility, efficacy, and selectivity. Carbon dots (CDs) have garnered interest for their small sizes (<10 nm), low toxicity, high water solubility, and bright fluorescence. This paper describes the use of CDs to improve drug vehiculation, stability, and chemotherapeutic efficiency of SN38 through a direct intracellular uptake in CRC. The covalent conjugation of SN38 to CDs via a carbamate bond provides a CD-SN38 hybrid material for slow, sustained, and pH-responsive drug release. CD-SN38 successfully penetrates the CRC cells with a release in the nucleus affecting first the cell cycle and then the cytoskeleton. Moreover, CD-SN38 leads to a deregulation of the extracellular matrix (ECM), one of the major components of the cancer niche considered a possible target therapy for reducing the cancer progression. This work shows the combined therapeutic and imaging potential of CD-based hybrid materials for the treatment of CRC. Future efforts for targeted therapy of chronic diseases characterized by altered ECM deposition, such as chronic kidney disease and chronic allograft nephropathy in kidney transplant patients are envisaged.http://www.sciencedirect.com/science/article/pii/S2590006422000849Carbon dotsColorectal cancer therapyDrug deliverySN38Cell cycleExtracellular matrix |
| spellingShingle | Deborah Mattinzoli Michele Cacioppo Masami Ikehata Silvia Armelloni Carlo Maria Alfieri Giuseppe Castellano Mario Barilani Francesca Arcudi Piergiorgio Messa Maurizio Prato Carbon dots conjugated to SN38 for improved colorectal anticancer therapy Materials Today Bio Carbon dots Colorectal cancer therapy Drug delivery SN38 Cell cycle Extracellular matrix |
| title | Carbon dots conjugated to SN38 for improved colorectal anticancer therapy |
| title_full | Carbon dots conjugated to SN38 for improved colorectal anticancer therapy |
| title_fullStr | Carbon dots conjugated to SN38 for improved colorectal anticancer therapy |
| title_full_unstemmed | Carbon dots conjugated to SN38 for improved colorectal anticancer therapy |
| title_short | Carbon dots conjugated to SN38 for improved colorectal anticancer therapy |
| title_sort | carbon dots conjugated to sn38 for improved colorectal anticancer therapy |
| topic | Carbon dots Colorectal cancer therapy Drug delivery SN38 Cell cycle Extracellular matrix |
| url | http://www.sciencedirect.com/science/article/pii/S2590006422000849 |
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