A future where cancer treatment is transformed by advanced technology is rapidly approaching. Innovative strategies employing therapeutic nucleic acids, essential molecules instructing cells to combat diseases like cancer, are paving this path. The challenge has been delivering these molecules inside cells, akin to passing a secret message through impregnable walls. This isn’t mere speculation but the essence of a recent breakthrough. Tiny, specialized carriers known as nanoscale metal-organic frameworks (nanoMOFs) have been crafted to transport these crucial molecules directly into the heart of cancer cells, navigating past natural defenses that have long been an obstacle. Moving beyond merely delivering the message, this method ensures it reaches the right recipient, heralding focused cancer treatments devoid of traditional therapy side effects. This significant advancement will change the battle against cancer, marking a pioneering moment in gene therapy.

In a pioneering study led by lead authors Dr. Ruxandra Gref from Université Paris-Saclay and Dr. Kirill Afonin from the University of North Carolina at Charlotte, alongside their team comprising Dr. Juan Casas-Solvas and Professor Antonio Vargas-Berenguel from the University of Almería, Dr. Gilles Patriarche also from Université Paris-Saclay, and Sandra Arroyo-Becker, Yelixza I. Avila, Dr. Morgan Chandler from the University of North Carolina at Charlotte, and Dr. Xue Li from Université Paris-Saclay, a novel method for treating cancer has been revealed in the International Journal of Pharmaceutics: X, showing the vast potential of nanoscale metal-organic frameworks (nanoMOFs) in gene therapy. This groundbreaking research demonstrates how nanoMOFs can deliver therapeutic nucleic acids directly to cancer cells, opening new doors in the fight against this widespread disease.

The approach uses engineered nanoMOFs to package and send therapeutic nucleic acids into cancer cells. This tackles a significant challenge in gene therapy: getting the negatively charged nucleic acids through the cell membrane. These carefully designed nanoMOFs not only overcome this barrier but also enable the targeting of specific cancer cells, boosting the effectiveness of the treatment.

Dr. Afonin sheds light on their findings, “We have successfully utilized engineered nanoMOFs, developed by Ruxandra Gref’s team, to deliver therapeutic nucleic acids into cancer cells, as evidenced by a noticeable reduction in reporter gene expression in MDA-MB-231 breast cancer cells via RNA interference.” This breakthrough opens the door to more effective cancer treatments by allowing the targeted delivery of genetic material directly to tumor cells.

The research team employed sophisticated methods to develop and evaluate the nanoMOFs, beginning with their synthesis through microwave-assisted processes using iron chloride and benzene-1,3,5-tricarboxylic acid. Subsequent modifications enhanced the nanoMOFs’ surface to target cancer cells more effectively, notably by introducing P-CD-M to boost cell affinity. Preparing the nucleic acids for integration into the nanoMOFs was a meticulous step involving multiple optimization protocols to achieve optimal protection of nucleic acid cargos and preserve their integrity, ensuring their effectiveness upon delivery. Characterization of the nanoMOFs, through dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA), confirmed their appropriate size, stability, and successful nucleic acid loading, validating their potential for real-world applications.

Several tests were conducted to verify the effectiveness of the nanoMOFs, including studies on how well the nanoMOFs were taken up by cells and their ability to silence specific genes. These tests showed the nanoMOFs’ capability to effectively enter cancer cells and deliver their nucleic acid cargos, leading to the desired therapeutic effects.

The implications of this research are significant, offering a promising new path for cancer treatment. By allowing for the precise delivery of therapeutic nucleic acids to tumor cells, nanoMOFs have the potential to enhance the accuracy and efficiency of gene therapy, minimizing side effects and improving outcomes for patients. Dr. Afonin highlights, “Combining different therapeutic agents resulted in a more significant therapeutic effect,” underscoring the potential for using nanoMOFs in combination therapies for better results.

This innovative work lays the groundwork for further exploring and developing nanoMOF-based treatments. More comprehensive structure-function studies are needed to expand upon the current platform, indicating the future direction of this exciting area of research. The successful application of nanoMOFs in gene therapy could transform cancer treatment, offering new hope to millions of patients worldwide. In conclusion, Dr. Gref and Dr. Afonin’s study reveals that nanoMOFs offer a new avenue for cancer treatment, efficiently delivering nucleic acid therapies to targeted cells and enhancing treatment efficacy. Their research, confirming nanoMOFs’ protective and delivery capabilities, underscores the potential for innovative, less invasive treatments.


X. Li et al., “Nanoscale metal-organic frameworks for the delivery of nucleic acids to cancer cells,” International Journal of Pharmaceutics: X 5 (2023) 100161. DOI: https://doi.org/10.1016/j.ijpx.2023.100161.