Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging

Abstract Manganese-based metal–organic frameworks (Mn MOFs) represent a highly promising class of materials, characterized by their low toxicity, oxidative capabilities, and biocompatibility, which render them particularly advantageous for various biomedical applications. This study presents the dev...

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Main Authors: Mahsa Nazari, Mina Alikhani, Hamed Tabasi, Sirous Nekooei, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani, Mona Alibolandi
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Cancer Nanotechnology
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Online Access:https://doi.org/10.1186/s12645-025-00333-2
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author Mahsa Nazari
Mina Alikhani
Hamed Tabasi
Sirous Nekooei
Khalil Abnous
Seyed Mohammad Taghdisi
Mohammad Ramezani
Mona Alibolandi
author_facet Mahsa Nazari
Mina Alikhani
Hamed Tabasi
Sirous Nekooei
Khalil Abnous
Seyed Mohammad Taghdisi
Mohammad Ramezani
Mona Alibolandi
author_sort Mahsa Nazari
collection DOAJ
description Abstract Manganese-based metal–organic frameworks (Mn MOFs) represent a highly promising class of materials, characterized by their low toxicity, oxidative capabilities, and biocompatibility, which render them particularly advantageous for various biomedical applications. This study presents the development of a biodegradable, intelligent carrier utilizing MOFs with Mn center and 4,4'-dithiobisbenzoic acid ligands that responds to pH changes and glutathione levels for targeted chemodynamic therapy. The synthesized nanoparticles demonstrated remarkable encapsulation efficiency and a doxorubicin hydrochloride (DOX) loading capacity of 84.95 ± 1.7%. To improve biocompatibility, the DOX-loaded manganese metal–organic frameworks (Mn MOFs) were encapsulated with macrophage cells (RAW 264.7) membranes (MCM). The Sgc8-c DNA aptamer, known for its specific targeting of the PTK7 receptor, was integrated into the formulation to develop the Apt–Mn MOF–DOX–MCM. In vitro studies indicated that the Mn MOFs degrade into Mn2+ ions under acidic and high glutathione conditions, promoting DOX release and initiating a Fenton-like reaction to improve therapeutic efficacy. The Apt–Mn MOF–DOX–MCM formulation exhibited increased cytotoxicity, enhanced cellular uptake, and efficiently inhibited colony formation in PTK7-overexpressing B16F0 cancer cells. Preclinical studies revealed that this targeted system significantly reduced tumor size in B16F0 tumor-bearing C57BL/6 mice compared to non-targeted formulations. Furthermore, both Apt–Mn MOF–DOX–MCM and Mn MOF–DOX–MCM showed potential as MRI contrast agents, with favorable accumulation at tumor sites. In conclusion, the developed platform represents a promising theranostic approach, integrating diagnostic imaging with targeted drug delivery for improved cancer treatment.
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spelling doaj-art-7982d8f5eff04311aa77d2e2d07c0fd92025-08-20T02:37:13ZengBMCCancer Nanotechnology1868-69581868-69662025-06-0116112610.1186/s12645-025-00333-2Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imagingMahsa Nazari0Mina Alikhani1Hamed Tabasi2Sirous Nekooei3Khalil Abnous4Seyed Mohammad Taghdisi5Mohammad Ramezani6Mona Alibolandi7Department of Chemistry, Faculty of Science, Ferdowsi University of MashhadPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesDepartment of Radiology, Faculty of Medicine, Mashhad University of Medical SciencesPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesAbstract Manganese-based metal–organic frameworks (Mn MOFs) represent a highly promising class of materials, characterized by their low toxicity, oxidative capabilities, and biocompatibility, which render them particularly advantageous for various biomedical applications. This study presents the development of a biodegradable, intelligent carrier utilizing MOFs with Mn center and 4,4'-dithiobisbenzoic acid ligands that responds to pH changes and glutathione levels for targeted chemodynamic therapy. The synthesized nanoparticles demonstrated remarkable encapsulation efficiency and a doxorubicin hydrochloride (DOX) loading capacity of 84.95 ± 1.7%. To improve biocompatibility, the DOX-loaded manganese metal–organic frameworks (Mn MOFs) were encapsulated with macrophage cells (RAW 264.7) membranes (MCM). The Sgc8-c DNA aptamer, known for its specific targeting of the PTK7 receptor, was integrated into the formulation to develop the Apt–Mn MOF–DOX–MCM. In vitro studies indicated that the Mn MOFs degrade into Mn2+ ions under acidic and high glutathione conditions, promoting DOX release and initiating a Fenton-like reaction to improve therapeutic efficacy. The Apt–Mn MOF–DOX–MCM formulation exhibited increased cytotoxicity, enhanced cellular uptake, and efficiently inhibited colony formation in PTK7-overexpressing B16F0 cancer cells. Preclinical studies revealed that this targeted system significantly reduced tumor size in B16F0 tumor-bearing C57BL/6 mice compared to non-targeted formulations. Furthermore, both Apt–Mn MOF–DOX–MCM and Mn MOF–DOX–MCM showed potential as MRI contrast agents, with favorable accumulation at tumor sites. In conclusion, the developed platform represents a promising theranostic approach, integrating diagnostic imaging with targeted drug delivery for improved cancer treatment.https://doi.org/10.1186/s12645-025-00333-2Metal–organic frameworksDoxorubicinMacrophage cell membraneFenton-like reactionSgc8-c aptamerMRI
spellingShingle Mahsa Nazari
Mina Alikhani
Hamed Tabasi
Sirous Nekooei
Khalil Abnous
Seyed Mohammad Taghdisi
Mohammad Ramezani
Mona Alibolandi
Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging
Cancer Nanotechnology
Metal–organic frameworks
Doxorubicin
Macrophage cell membrane
Fenton-like reaction
Sgc8-c aptamer
MRI
title Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging
title_full Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging
title_fullStr Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging
title_full_unstemmed Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging
title_short Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging
title_sort dual responsive manganese based metal organic framework coated with aptamer tagged macrophage membrane an innovative approach for enhanced chemodynamic therapy and mr imaging
topic Metal–organic frameworks
Doxorubicin
Macrophage cell membrane
Fenton-like reaction
Sgc8-c aptamer
MRI
url https://doi.org/10.1186/s12645-025-00333-2
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