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Nanosized biligated metal-organic framework systems for enhanced cellular and mitochondrial sequential targeting of
Kholoud K Arafa1, Mostafa Fytory1, Shaker A Mousa2
1Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, Giza 12578, Egypt. ielsherbiny@zewailcity.edu.eg.
Abstract:
Mitochondria are reported to play a paramount role in tumorigenesis which positions them as an instrumental druggable target. However, selective drug delivery to cancer-localized mitochondria remains challenging. Herein, we report for the first time, the design, development and evaluation of a hepatic cancer-specific mitochondria-targeted dual ligated nanoscale metal-organic framework (NMOF) for cellular and mitochondrial sequential drug delivery. Surface functionalization was performed through covalent-linking of folic acid and triphenylphosphonium moieties to the aminated Zr-based MOF, NH2-UiO-66. The characterization of the dual-ligated NMOFs using XRD, FTIR, DSC and BET analysis proved the successful conjugation process. Assessment of the drug loading and release profiling of doxorubicin (DOX)-loaded NMOF confirmed the proper retention of the drug within the NMOF porous structure alongside enhanced release in the tumor acidic environment. Furthermore, biological evaluation of the anti-tumor activity of the DOX-loaded dual-ligated NMOF on hepatocellular carcinoma affirmed the superiority of the developed system in killing the cancerous cells via apoptosis induction and halting cell cycle progression. This study attempts to underscore the promising potential of surface functionalized NMOFs in developing anticancer drug delivery systems to achieve targeted therapy.
Insights
Researchers developed a novel dual-ligated nanoscale metal-organic framework (NMOF) for targeted drug delivery to mitochondria in liver cancer. This NMOF system effectively delivers doxorubicin (DOX), enhancing anti-cancer efficacy and apoptosis induction.
Area of Science:
- Nanotechnology
- Materials Science
- Oncology
Background:
- Mitochondria play a critical role in cancer development, making them a key therapeutic target.
- Selective drug delivery to mitochondria in cancer cells presents a significant challenge in oncology.
Purpose of the Study:
- To design and evaluate a dual-ligated nanoscale metal-organic framework (NMOF) for targeted drug delivery to mitochondria in hepatic cancer.
- To achieve sequential cellular and mitochondrial drug delivery for enhanced therapeutic outcomes.
Main Methods:
- Fabrication of a dual-ligated NMOF by covalently linking folic acid and triphenylphosphonium to an aminated Zr-based MOF (NH2-UiO-66).
- Characterization using XRD, FTIR, DSC, and BET analysis to confirm successful conjugation.
- Loading doxorubicin (DOX) into the NMOF and evaluating its release profile under acidic tumor conditions.
- Assessing the anti-tumor activity of DOX-loaded NMOF on hepatocellular carcinoma cells.
Main Results:
- Successful synthesis and characterization of dual-ligated NMOFs with confirmed drug loading and retention.
- Enhanced DOX release from NMOFs in acidic tumor microenvironments.
- Demonstrated superior anti-tumor activity of DOX-loaded NMOF against hepatocellular carcinoma, inducing apoptosis and cell cycle arrest.
Conclusions:
- Surface-functionalized NMOFs show significant promise for targeted cancer therapy by enabling sequential drug delivery to mitochondria.
- The developed dual-ligated NMOF system offers a potential strategy for overcoming challenges in mitochondrial drug delivery for liver cancer treatment.
