Professor Moein Moghimi, School of Pharmacy, Newcastle University, UK

Mechanisms and Barriers in Nanomedicine: Addressing Integrated Challenges, Offering Potential Solutions

Today, healthcare is harnessing the power of genomics, gene editing and nanotechnology to build a solid foundation for a more patient-centric and individualized approach to healthcare and improving clinical outcomes. Indeed, technological breakthroughs in targeted drug delivery and nanomedicine together with advances in biomarker discovery are becoming the driving force of precision medicine.

Despite remarkable progress in nanomedicine, like other nascent technologies, nanomedicine has followed a Garner Hype Cycle course. This is described as an initial sharp rise of expectations, a trough of disillusionment and the “slope of enlightenment”. This cycle has sparked a flurry of debate and generated a mixed perception of nanomedicine research. This talk will feature a personal view of the progress in overcoming integrated barriers (formulation, immunological, cellular, clinical and regulatory barriers) in nanomedicine. Indeed, an effective treatment planning must not only consider disease heterogeneity, but also the broader aspects of disease microenvironment as therapy progresses. These include the dynamics of immune system microenvironment, and rate-limiting biological barriers and transport processes in relation to spatiotemporal performance of nanomedicine.

To address the aforementioned challenges systems approaches are needed. The presentation will introduce work in progress towards development of more effective and safer vehicles and therapeutic nanoplatforms than lipid nanoparticles for crossing the biological barriers, global solutions to nanoparticle-mediated adverse immune reactions, and biomarker detection technologies.

References

1. L.-P. Wu, D. Ahmadvand, J. Su, A. Hall, X. Tan, Z.S. Farhangrazi, S.M. Moghimi, Crossing the blood-brain-barrier with nanoligand drug carriers self-assembled from a phage display peptide, Nature Communications 10 (2019) 4635.
2. S.M. Moghimi, D. Simberg, A. Anchordoquy, Tuning the engines of nanomedicine, Molecular Therapy 28 (2020) 693–694.
3. L.-P. Wu, M. Ficker, J.B. Christensen, D. Simberg, P.N. Trohopoulos, S.M. Moghimi, Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking, Nature Communications 12 (2021) 4858.
4. S.M. Moghimi, H.B. Haroon, A. Yaghmur, A.C. Hunter, E. Papini, Z.S. Farhangrazi, D. Simberg, P.N. Trohopoulos, Perspectives on complement and phagocytic cell responses to nanoparticles: from fundamentals to adverse reactions, Journal of Controlled Release 356 (2023) 115–129.
5. Y. Li, S. Jacques, H. Gaikwad, G. Wang, N.K. Banda, V.M. Holers, R.I. Scheinman, S. Tomlinson, S.M. Moghimi, D. Simberg, Inhibition of acute complement responses towards bolus-injected nanoparticles using targeted short-circulating regulatory proteins, Nature Nanotechnology (2014) doi.org/10.1038/s41565-023-01514-z