Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer

Ayuob Aghanejad; Shiva Kheiriabad; Maryam Ghaffari; Simin Namvar Aghdash; Neda Ghafouri; Jafar Ezzati Nazhad Dolatabadi; Hashem Andishmand; Michael R. Hamblin

doi:10.1038/s41598-024-82074-7

Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer

Ayuob Aghanejad, Shiva Kheiriabad, Maryam Ghaffari, Simin Namvar Aghdash, Neda Ghafouri, Jafar Ezzati Nazhad Dolatabadi, Hashem Andishmand, Michael R. Hamblin

Laser Research Centre

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1813
Journal	Scientific Reports
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41598-024-82074-7
Publication status	Published - Dec 2025

Keywords

Curcumin
Methotrexate
Nanocomplex
PAMAM dendrimer

ASJC Scopus subject areas

Multidisciplinary

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-024-82074-7

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Aghanejad, A., Kheiriabad, S., Ghaffari, M., Namvar Aghdash, S., Ghafouri, N., Ezzati Nazhad Dolatabadi, J., Andishmand, H., & Hamblin, M. R. (2025). Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer. Scientific Reports, 15(1), Article 1813. https://doi.org/10.1038/s41598-024-82074-7

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title = "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 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.",

keywords = "Curcumin, Methotrexate, Nanocomplex, PAMAM dendrimer",

author = "Ayuob Aghanejad and Shiva Kheiriabad and Maryam Ghaffari and {Namvar Aghdash}, Simin and Neda Ghafouri and {Ezzati Nazhad Dolatabadi}, Jafar and Hashem Andishmand and Hamblin, {Michael R.}",

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doi = "10.1038/s41598-024-82074-7",

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Aghanejad, A, Kheiriabad, S, Ghaffari, M, Namvar Aghdash, S, Ghafouri, N, Ezzati Nazhad Dolatabadi, J, Andishmand, H & Hamblin, MR 2025, 'Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer', Scientific Reports, vol. 15, no. 1, 1813. https://doi.org/10.1038/s41598-024-82074-7

TY - JOUR

T1 - Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer

AU - Aghanejad, Ayuob

AU - Kheiriabad, Shiva

AU - Ghaffari, Maryam

AU - Namvar Aghdash, Simin

AU - Ghafouri, Neda

AU - Ezzati Nazhad Dolatabadi, Jafar

AU - Andishmand, Hashem

AU - Hamblin, Michael R.

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

KW - Curcumin

KW - Methotrexate

KW - Nanocomplex

KW - PAMAM dendrimer

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U2 - 10.1038/s41598-024-82074-7

DO - 10.1038/s41598-024-82074-7

M3 - Article

C2 - 39805840

AN - SCOPUS:85215597229

SN - 2045-2322

VL - 15

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 1813

ER -

Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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