Announcements

1. Congratulations on receiving the Pharmaceuticals Best Paper Award! To start, could you briefly introduce yourself and tell us about the winning paper—its title, focus, and the main question you sought to answer?

Chih Hung: I am an Assistant Professor in the Department of Biology and the Interdisciplinary Neuroscience Program at Syracuse University. My research focuses on understanding the mechanisms that drive neurological diseases, particularly how neuroinflammation, pathological protein aggregation, and autophagy–lysosomal dysfunction interact to cause damage to brain cells. We then use these mechanistic insights to identify and develop therapeutic strategies, including small molecules, peptides, and nanoparticle-based approaches. A recurring challenge is getting these therapies across the brain and to the right cells and specific targets, which has led us to study the blood–brain barrier (BBB) as an important determinant of therapeutic efficacy.

Jialiu: I am an Assistant Professor in the Department of Biomedical and Chemical Engineering and the Interdisciplinary Neuroscience Program at Syracuse University. My research focuses on engineering nanomedicines and drug-delivery systems to overcome physiological barriers and control where therapeutics go in the body. We use polymer chemistry, biomaterials engineering, and nanotechnology to design nanoparticles with defined properties for tissue, cellular, and intracellular targeting. For me, the BBB is a particularly interesting engineering challenge because nanoparticle size, composition, surface chemistry, and targeting ligands can be deliberately tuned to control how these materials interact with the barrier and where they go after reaching the brain.

Both: We are grateful to the selection committee for recognizing our review article, “Blood–Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience” with the Best Paper Award. Our article focuses on one of the major challenges in treating neurological diseases: how to effectively deliver therapeutic agents across the BBB and into the brain. Specifically, we examined nanoparticles as a versatile and promising approach for overcoming this barrier. We explored how nanoparticle properties and surface modifications influence BBB targeting and penetration, while also considering BBB models and disease-associated changes that could be leveraged to improve delivery. At the core of the paper was a broader question: How can we better understand and engineer nanoparticles to achieve more effective and precise interactions with the BBB while ultimately moving these technologies closer to clinical translation for neurological diseases? We hope this review helps connect advances in biomaterials and nanotechnology with the biological complexity of the BBB and encourages the development of next-generation nanoparticle-based therapeutics.

2. What inspired this particular study? Was it part of a larger research program, or did it stem from a specific observation or question that arose unexpectedly?

Chih Hung: For me, this study was motivated by a question that comes up repeatedly in our research: we can identify promising disease mechanisms and molecular targets and develop new therapeutic strategies, but how do we get these therapies to the right place in the brain to effectively treat neurological diseases? If we want to translate mechanistic discoveries into meaningful treatments, drug delivery becomes an essential part of the problem. This led me to think about the BBB not simply as a wall that needs to be crossed, but as a dynamic biological interface that changes with disease state and progression. This perspective inspired us to highlight the importance of considering BBB accessibility early in therapeutic design, whether we are developing small molecules, peptides, or nanoparticle-based therapies, and to emphasize that effective brain delivery should be considered alongside the therapeutic mechanisms.

Jialiu: I have spent much of my career engineering nanoparticles to overcome biological and physiological barriers and thinking about what happens once they reach their destination. Small changes in particle size, surface chemistry, composition, or architecture can substantially alter how a nanoparticle interacts with a biological system. So, when we started discussing the BBB, the engineering question was: if the barrier is so complex and dynamic, how do we design the nanoparticle around it? At the same time, research on nanoparticles for BBB targeting and brain drug delivery was expanding rapidly, with a wide range of nanoparticle designs, targeting strategies, and experimental models being explored. Understanding how these different design features influence BBB targeting and identifying principles that can be applied across different systems was exactly what motivated us to write this review.

Both: This study was driven naturally out of our broader interdisciplinary research at the intersection of neuroscience, biomaterials, nanomedicine, and drug discovery. This intersection of our expertise, together with our interest in fostering new collaborations across disciplines, ultimately inspired us to write this article and explore how we can more rationally design nanoparticle-based strategies for precise and effective delivery to the brain.

3. The selection committee recognized your paper for its significant contribution to pharmaceutical research. In your view, what is the most important finding or advancement that this paper brings to the field—whether in drug discovery, mechanism of action, or therapeutic application?

Chih Hung: From a biological perspective, one of the important contributions of this review is highlighting that effective BBB-targeted delivery requires a deeper understanding of the BBB as a dynamic biological interface. We examined how the BBB changes across different disease states, how these changes can influence nanoparticle transport, and how different in vitro and in vivo models capture these complexities. This perspective emphasizes that successful brain delivery cannot be considered independently of the underlying biology and disease context.

Jialiu: From an engineering perspective, our article brings together the growing body of work on how nanoparticle properties, including size, composition, surface chemistry, and targeting strategies, can be deliberately engineered to interact with the BBB. Rather than focusing on any single nanoparticle system, we sought to identify broader design principles that can explain why particular approaches work in different contexts. The important question is therefore not “which nanoparticle works best?” but “which design is best suited to a specific barrier, disease, and therapeutic target?”

Both: We believe the broader contribution of this review is that it connects two perspectives that are often considered separately—the biology of the BBB and the engineering of therapeutic delivery systems—and places them within a common translational context. Rather than viewing BBB penetration simply as a technical challenge to overcome, we highlight the importance of understanding the interaction between the biological environment, nanoparticle design, and therapeutic goals. The article was therefore both an opportunity to synthesize what the field has learned so far and to identify the key questions and design principles that we believe will shape the next generation of brain drug-delivery strategies.

4. Every impactful paper has a backstory. Could you walk us through the key moments in this study’s development—from the initial idea, through the experimental work, to the final manuscript?

Chih Hung: As discussed earlier, this review was developed from a recurring challenge in our research: how do we get promising therapies across the brain? As we explored the BBB more extensively, I realized that understanding brain delivery requires more than thinking about the BBB as a physiological barrier, as we also need to understand how it is altered in neurological diseases and how those changes might influence therapeutic delivery. As a biologist and neuroscientist, I felt that incorporating a clinician–scientist’s perspective was essential to understanding the BBB in the context of human disease and clinical relevance. This was what led us to bring Dr. Evridiki Asimakidou into the project, whose clinical expertise helped us think more deeply about how BBB dysfunction varies across neurological diseases and what these changes might mean for translating nanoparticle-based delivery strategies.

Jialiu: From the engineering side, I was thinking about a complementary challenge: even if we develop a nanoparticle with promising BBB-targeting properties, how do we know whether it will actually work in a biologically relevant setting? The choice of experimental model can have a major influence on how we interpret nanoparticle transport and efficacy, so I realized that we needed to bring in synergistic expertise to develop and evaluate models that better capture the physiological properties of the BBB and other biological barriers. This led us to bring Dr. Justin Tan onboard, whose expertise in microfluidic and in vitro models provided an important engineering perspective on how we can more rigorously evaluate nanoparticle–BBB interactions and better bridge the gap between simplified laboratory models and physiological conditions.

Both: Once the four of us came together, the review evolved through a very iterative process of reading the literature, discussing different findings, and challenging one another’s perspectives. We kept asking questions such as: What can we learn from this study beyond this particular nanoparticle, model, or disease context? What biological features are actually important for delivery, and how well do the experimental models capture them? Those discussions shaped the article around nanoparticle properties and targeting strategies, BBB models, disease-associated changes, and ultimately therapeutic translation. Although this was a review article rather than an experimental study, there was still a process that felt almost like an experiment where we brought together four different perspectives and used them to test, challenge, and refine how we think about the field. The final manuscript therefore reflects not just a synthesis of the literature, but the collective thinking that emerged from bringing together biology, engineering, modeling, and clinical perspectives.

5. Were there particular challenges or hurdles you encountered while conducting this research? How did your team overcome them?

Chih Hung: One challenge was that the field does not always speak the same language. Different studies can use very different definitions of BBB penetration, brain delivery, or targeting, and a result described as successful in one study may be evaluated very differently in another. We also found that the biological context matters a lot where results from in vitro models do not necessarily tell us what will happen in neurodegenerative brains. So, one of the hardest challenges was making meaningful comparisons without forcing the literature into conclusions that the evidence did not really support.

Jialiu: I think the same issue came through very strongly from the materials side. Two nanoparticles may both be described as “BBB-targeting”, but they can differ substantially in composition, size, surface properties, targeting ligands, and transport mechanism. Even small differences in experimental design can change the outcome. We therefore had to look carefully at the details behind each finding rather than accepting those conclusions without further scrutiny. In many cases, we had to go back to the original studies and ask: What was actually measured? How was it measured? And what can we reasonably conclude from the results?

Both: That really encouraged us to be quite deliberate about how we interpreted the literature. We focused on the strength and context of the evidence, and we tried to distinguish findings that were supported across multiple systems from observations that were more model-specific. We also looked across the field, from basic nanoparticle design all the way to preclinical and clinical studies, which helped us see where the evidence was strong and where important gaps remained. In the end, the challenge was not just collecting information but assessing how each piece of evidence should be interpreted and how to connect findings that came from very different experimental settings. We think this systematic approach made the review more informative and actionable, because it highlights not only what we know about BBB-targeted delivery, but also where important gaps remain in the field, such as the need for more physiologically relevant models, more reliable and comprehensive measurements, and more rigorous comparisons across different strategies.

6. Finally, what message would you like to share with the Pharmaceuticals community—readers, future authors, and fellow researchers—as our newly recognized Best Paper Award winners?

Chih Hung: We sincerely appreciate the Pharmaceuticals editorial team, selection committee, and the community for recognizing our work. If I could leave the field with one message, it would be that the next generation of drug delivery needs to interact with the biology we are trying to change. In neurological disease, there is profound heterogeneity—across disease states, among cell types, and even within intracellular compartments and organelles. Understanding this heterogeneity is essential for defining what successful delivery actually means and determining where, when, and in which cells a therapeutic needs to act. I think we are at an exciting point because the tools are finally catching up with the questions: iPSC-derived human cells, organoids, super-resolution imaging, and increasingly sophisticated single-cell, single-organelle, and spatial omics now allow us to ask where a therapeutic goes, which cells and compartments it reaches, and what it actually changes. Together, these technologies give us an opportunity to connect disease mechanisms with drug delivery at a level of resolution that was previously difficult to achieve.

Jialiu: And from the engineering side, this opens up a very different way of thinking about nanomedicine. We do not have to view nanoparticles simply as carriers designed to deliver more drug to a particular tissue. Instead, we can target a particular cell type, organelle, or molecular pathway and tailor the material properties to achieve a defined biological effect. This perspective is increasingly shaping our own research. We are interested in developing specialized delivery systems that can actively interact with defined biological environments and help restore disease-associated dysfunction, rather than simply transporting a therapeutic agent. I think the combination of more human-relevant models, advanced imaging and omics technologies, and increasingly sophisticated materials engineering gives us an opportunity to move beyond empirical optimization toward more rational, biologically informed design.

Both: And perhaps most importantly, we don’t think the hardest problems in brain drug delivery can be solved within one discipline. The next advances will come from integrating neurobiology, materials science, drug delivery, clinical medicine, and quantitative technologies from the very beginning. Better tools alone will not be enough, and we need to ask better questions and design the experiments and delivery systems around the biological problem. For us, this review was one step in that direction. Looking ahead, we hope the field will move beyond simply asking “does it reach the brain?” and instead explore “where does it go, why does it go there, what does it change, and does that change actually improve the disease?”. Overall, we think about brain delivery as a continuum of processes rather than a single transport event. This shift, from viewing delivery as a technical endpoint to recognizing it as an integral part of therapeutic design, is where we see the greatest opportunity for developing more precise, functional, and ultimately translatable nanomedicines.