μMESH Implants: Advancing Glioblastoma Treatment with Controlled Drug Delivery

Significance

Glioblastoma is an aggressive and often fatal brain cancer. Despite significant progress in cancer treatment, glioblastoma remains one of the least curable forms of cancer, with a 5-year survival rate of only 5%. The current standard of care, known as the Stupp’s protocol, has not seen substantial improvements in over two decades and is associated with various therapy-induced complications The unique characteristics of glioblastoma, such as the presence of the blood-brain barrier and the thick extracellular matrix, as well as its biological heterogeneity, pose significant hurdles to effective treatment. These factors limit the delivery and distribution of therapeutic agents to the tumor site and contribute to the rapid recurrence of the disease. Therefore, the development of innovative drug delivery systems for local and regional therapies is of utmost importance. A new study conducted by Italian Institute of Technology scientists: Dr. Daniele Di Mascolo, Dr. Irene Guerriero, Dr. Cristiano Pesce, Dr. Raffaele Spanò, Dr. Anna Lisa Palange, and led by Dr. Paolo Decuzzi, introduced a promising approach in addressing the formidable challenge of treating glioblastoma. The research work is now published in the Journal ACS Nano. The authors developed μMESH, a mechanically conformable, biodegradable implant designed to address these challenges. μMESH consists of a polyvinyl alcohol (PVA) microlayer supporting a poly(lactic-co-glycolic acid) (PLGA) micronetwork. It offers precise control over its geometrical attributes, allowing for customization based on specific therapeutic requirements. Importantly, μMESH can carry a variety of therapeutic agents, including hydrophobic and water-soluble drugs.

The researchers evaluated four different μMESH configurations, each loaded with highly potent cytotoxic molecules, docetaxel (DTXL), and paclitaxel (PTXL), either in their native molecular form or as nanomedicines encapsulated within conventional spherical polymeric nanoparticles. The research conducted thorough physicochemical, pharmacological, and biological characterizations to optimize these μMESH-based formulations. One of the key findings of the study was the efficient loading of drugs into μMESH, with DTXL showing higher encapsulation efficiency than PTXL. This can be attributed to differences in drug solubility in the solvents used during device fabrication. The release profiles of these drugs from μMESH were also examined, with DTXL demonstrating a faster initial release rate compared to PTXL. This burst release is essential for targeting rapidly dividing malignant cells. Furthermore, the authors discussed the cytotoxicity of these drug-loaded μMESH configurations using both monolayer cultures and 3D tumor spheroids, which better mimic the in vivo tumor microenvironment. The results demonstrated the potency of DTXL over PTXL, consistent with existing knowledge. Importantly, μMESH loaded with DTXL was found to be as effective as free DTXL in inducing cell death in 3D tumor spheroids. These findings suggest that μMESH has the potential to enhance the therapeutic efficacy of these drugs.

The research team demonstrated preclinical validation in orthotopic murine models of glioblastoma. The results indicated that μMESH-based therapies significantly prolonged the survival of treated mice compared to untreated controls. Notably, μMESH loaded with DTXL demonstrated particularly promising outcomes, with a substantial portion of the mice surviving beyond the 3-month observation period. In conclusion, the study’s findings suggest that μMESH, a deformable and biodegradable implant, has the potential to address some of the challenges associated with glioblastoma treatment. Its ability to provide sustained drug release over an extended period, coupled with its customizable design, makes it a promising platform for localized and regional therapies. While further research is needed to validate these findings and explore potential clinical applications, this study represents a significant step toward improving the prognosis for glioblastoma patients. The development of innovative drug delivery systems like μMESH offers hope for better outcomes in the fight against this devastating disease.

Revolutionizing Glioblastoma Treatment: μMESH Implants Unleash the Power of Sustained Drug Delivery - Medicine Innovates — Image Credit: ACS Nano 2023, 17, 15, 14572–14585

About the author

Dr. Paolo Decuzzi
Senior Researcher Tenured – Principal Investigator
Nanotechnology for Precision Medicine
Italian Institute of Technology

Paolo Decuzzi is a Senior Scientist and the Founding Director of the Laboratory of Nanotechnology for Precision Medicine at the Italian Institute of Technology in Genova – Italy.

Dr. Decuzzi earned his M.Sc. degree in Mechanical Engineering from the Polytechnic University of Bari (Italy) in 1997 and his Ph.D. degree in Mechanical Engineering from the University of Naples – Federico II (Italy) in 2001, with a thesis on friction and adhesion at the nanoscale. In 2002, he was nominated Assistant Professor of Machine Design at the Polytechnic University of Bari and, in 2005, he became Associate Professor in the School of Medicine of the University ‘Magna Graecia’ of Catanzaro. There, he co-founded BioNEM – the laboratory of BioNanotechnology and Engineering for Medicine – one of the first nano-engineering laboratories built in a School of Medicine, worldwide. In October 2007, he joined The University of Texas Health Science Center in Houston as an Associate Professor of Biomedical Engineering. In October 2010, he moved to the Houston Methodist Hospital where he served as a Professor of Biomedical Engineering till July 2015. There, he founded the Center for the Rational Design of Multifunctional Nanoconstructs, with the financial support of the Cancer Prevention and Research Center of Texas and the US National Cancer Institute; and served first as the co-Chair of the Nanomedicine Department and then as the interim Chair of the Translational Imaging Department. In July 2014, Dr. Decuzzi was awarded a European Research Council “Consolidator Grant” to design, synthesize and develop nanoconstructs for imaging and therapy in brain cancer. In July 2015, he joined the Italian Institute of Technology in Genova.

Dr. Decuzzi has been a visiting scientist at the Department of Theoretical and Applied Mechanics at the University of Michigan – Ann Arbor (1998, 1999 and 2001); and a visiting professor at the Princeton Materials Institute – Princeton (2003); the Heart and Lung Institute at the Ohio State University (2003 and 2004); the University of Texas Health Science Center (2006); and the Radiology Department at Stanford Medicine (2018, 2019, 2020, 2021).

Dr. Decuzzi has published over 180 papers in international peer-reviewed journals, international conferences, and book chapters. He holds over 5 patents in the field of Nanomedicine. He co-founded NEMB – NanoEngineering for Medicine and Biology – committee of the American Society for Mechanical Engineers and is involved in multiple dissemination activities to foster the collaboration between biomedical scientists and engineers. He serves on multiple NIH, NSF, ESF, and Italian Government study sections and his research activity has been primarily supported by NIH, DOD, CPRIT in USA; ESF and ERC in EU. In his career, he has so far secured over 15M€ in extramural funding, half of which from European grants.

Reference

Di Mascolo D, Guerriero I, Pesce C, Spanò R, Palange AL, Decuzzi P. μMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment. ACS Nano. 2023 Aug 8;17(15):14572-14585. doi: 10.1021/acsnano.3c01574.

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