Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer
Abstract The simultaneous administration of multiple drugs within identical nanocarriers to cancer cells or tissues can result in the effective action of drugs at reduced concentrations. In this investigation, PAMAM dendrimers (G4-PAMAM) were employed to link with methotrexate (MTX) using DCC/NHS ch...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82074-7 |
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| author | Ayuob Aghanejad Shiva Kheiriabad Maryam Ghaffari Simin Namvar Aghdash Neda Ghafouri Jafar Ezzati Nazhad Dolatabadi Hashem Andishmand Michael R. Hamblin |
| author_facet | Ayuob Aghanejad Shiva Kheiriabad Maryam Ghaffari Simin Namvar Aghdash Neda Ghafouri Jafar Ezzati Nazhad Dolatabadi Hashem Andishmand Michael R. Hamblin |
| author_sort | Ayuob Aghanejad |
| collection | DOAJ |
| description | Abstract The simultaneous administration of multiple drugs within identical nanocarriers to cancer cells or tissues can result in the effective action of drugs at reduced concentrations. In this investigation, PAMAM dendrimers (G4-PAMAM) were employed to link with methotrexate (MTX) using DCC/NHS chemistry and followed by the entrapment of curcumin (Cur) within it. The establishment of covalent bonds between MTX and the PAMAM dendrimer led to PAMAM-MTX interaction, verified and described through FT-IR. Various techniques were employed to evaluate the structural properties of the prepared Cur-PAMAM-MTX NC. The Cur-PAMAM-MTX NC, after preparation, exhibited a particle size of 249 nm, with an encapsulation efficiency (EE) of ~ 81% for Cur. The cumulative in vitro release of Cur-loaded NC indicated a controlled release influenced by time and pH. The cell study results revealed that Cur-PAMAM-MTX NC exhibited significantly higher cytotoxicity than free MTX, Cur, and other formulations tested in vitro. The synergistic effect of co-delivery of MTX and Cur by PAMAM significantly increased cytotoxicity. Besides, the significant ROS level rising has been shown in the treated cells with MTX-PAMAM-Cur. Considering these findings, the co-delivery NC shows promise for additional in vitro investigations and possesses the capacity to function as an effective framework for the combined delivery of MTX and Cur in cervical cancer chemotherapy. |
| format | Article |
| id | doaj-art-876ab36f6449486fbe5c16ff0fc82af9 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-876ab36f6449486fbe5c16ff0fc82af92025-01-19T12:17:26ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-024-82074-7Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancerAyuob Aghanejad0Shiva Kheiriabad1Maryam Ghaffari2Simin Namvar Aghdash3Neda Ghafouri4Jafar Ezzati Nazhad Dolatabadi5Hashem Andishmand6Michael R. Hamblin7Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical SciencesDepartment of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani UniversityPharmaceutical Analysis Research Center, Tabriz University of Medical SciencesDepartment of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani UniversityPharmaceutical Analysis Research Center, Tabriz University of Medical SciencesDrug Applied Research Center, Tabriz University of Medical SciencesResearch Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical SciencesLaser Research Centre, Faculty of Health Science, University of JohannesburgAbstract The simultaneous administration of multiple drugs within identical nanocarriers to cancer cells or tissues can result in the effective action of drugs at reduced concentrations. In this investigation, PAMAM dendrimers (G4-PAMAM) were employed to link with methotrexate (MTX) using DCC/NHS chemistry and followed by the entrapment of curcumin (Cur) within it. The establishment of covalent bonds between MTX and the PAMAM dendrimer led to PAMAM-MTX interaction, verified and described through FT-IR. Various techniques were employed to evaluate the structural properties of the prepared Cur-PAMAM-MTX NC. The Cur-PAMAM-MTX NC, after preparation, exhibited a particle size of 249 nm, with an encapsulation efficiency (EE) of ~ 81% for Cur. The cumulative in vitro release of Cur-loaded NC indicated a controlled release influenced by time and pH. The cell study results revealed that Cur-PAMAM-MTX NC exhibited significantly higher cytotoxicity than free MTX, Cur, and other formulations tested in vitro. The synergistic effect of co-delivery of MTX and Cur by PAMAM significantly increased cytotoxicity. Besides, the significant ROS level rising has been shown in the treated cells with MTX-PAMAM-Cur. Considering these findings, the co-delivery NC shows promise for additional in vitro investigations and possesses the capacity to function as an effective framework for the combined delivery of MTX and Cur in cervical cancer chemotherapy.https://doi.org/10.1038/s41598-024-82074-7CurcuminPAMAM dendrimerMethotrexateNanocomplex |
| spellingShingle | Ayuob Aghanejad Shiva Kheiriabad Maryam Ghaffari Simin Namvar Aghdash Neda Ghafouri Jafar Ezzati Nazhad Dolatabadi Hashem Andishmand Michael R. Hamblin Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer Scientific Reports Curcumin PAMAM dendrimer Methotrexate Nanocomplex |
| title | Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer |
| title_full | Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer |
| title_fullStr | Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer |
| title_full_unstemmed | Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer |
| title_short | Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer |
| title_sort | targeted co delivery nanosystem based on methotrexate curcumin and pamam dendrimer for improvement of the therapeutic efficacy in cervical cancer |
| topic | Curcumin PAMAM dendrimer Methotrexate Nanocomplex |
| url | https://doi.org/10.1038/s41598-024-82074-7 |
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