A step forward on the in vitro and in vivo assessment of a novel nanomedicine against melanoma
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved..
Melanoma is the most aggressive form of skin cancer, with increasing incidence and mortality rates. To overcome current treatment limitations, a hybrid molecule (HM) combining a triazene and a sulfur L-tyrosine analogue, was recently synthesized, incorporated in long blood circulating liposomes (LIP HM) and validated in an immunocompetent melanoma model. The present work constitutes a step forward in the therapeutic assessment of HM formulations. Here, human melanoma cells, A375 and MNT-1, were used and dacarbazine (DTIC), a triazene drug clinically available as first-line treatment for melanoma, constituted the positive control. In cell cycle analysis, A375 cells, after 24-h incubation with HM (60 μM) and DTIC (70 μM), resulted in a 1.2 fold increase (related to control) in the percentage of cells in G0/G1 phase. The therapeutic activity was evaluated in a human murine melanoma model (subcutaneously injected with A375 cells) to most closely resemble the human pathology. Animals treated with LIP HM exhibited the highest antimelanoma effect resulting in a 6-, 5- and 4-fold reduction on tumor volume compared to negative control, Free HM and DTIC groups, respectively. No toxic side effects were detected. Overall, these results constitute another step forward in the validation of the antimelanoma activity of LIP HM, using a murine model that more accurately simulates the pathology that occurs in human patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:640 |
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| Enthalten in: |
International journal of pharmaceutics - 640(2023) vom: 10. Juni, Seite 123011 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pinho, Jacinta O [VerfasserIn] |
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| Links: |
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| Themen: |
7GR28W0FJI |
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| Anmerkungen: |
Date Completed 29.05.2023 Date Revised 29.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2023.123011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Melanoma is the most aggressive form of skin cancer, with increasing incidence and mortality rates. To overcome current treatment limitations, a hybrid molecule (HM) combining a triazene and a sulfur L-tyrosine analogue, was recently synthesized, incorporated in long blood circulating liposomes (LIP HM) and validated in an immunocompetent melanoma model. The present work constitutes a step forward in the therapeutic assessment of HM formulations. Here, human melanoma cells, A375 and MNT-1, were used and dacarbazine (DTIC), a triazene drug clinically available as first-line treatment for melanoma, constituted the positive control. In cell cycle analysis, A375 cells, after 24-h incubation with HM (60 μM) and DTIC (70 μM), resulted in a 1.2 fold increase (related to control) in the percentage of cells in G0/G1 phase. The therapeutic activity was evaluated in a human murine melanoma model (subcutaneously injected with A375 cells) to most closely resemble the human pathology. Animals treated with LIP HM exhibited the highest antimelanoma effect resulting in a 6-, 5- and 4-fold reduction on tumor volume compared to negative control, Free HM and DTIC groups, respectively. No toxic side effects were detected. Overall, these results constitute another step forward in the validation of the antimelanoma activity of LIP HM, using a murine model that more accurately simulates the pathology that occurs in human patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Caspase 3/7 activity | |
| 650 | 4 | |a Cell cycle arrest | |
| 650 | 4 | |a Hybrid molecule | |
| 650 | 4 | |a In vitro cell models | |
| 650 | 4 | |a In vivo melanoma nude model | |
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| 650 | 4 | |a Melanoma | |
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| 700 | 1 | |a Godinho-Santos, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Amaral, Joana D |e verfasserin |4 aut | |
| 700 | 1 | |a Mendes, Eduarda |e verfasserin |4 aut | |
| 700 | 1 | |a Perry, Maria Jesus |e verfasserin |4 aut | |
| 700 | 1 | |a Francisco, Ana Paula |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigues, Cecília M P |e verfasserin |4 aut | |
| 700 | 1 | |a Gaspar, M Manuela |e verfasserin |4 aut | |
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