Venturing into the cutting-edge field where tiny technology meets body defense mechanisms, researchers are exploring new ways to improve how we heal and prevent diseases. They’re focusing on creating minuscule, thread-like particles that can communicate with our body’s defense system in a way that could make future medical treatments not only more effective but also free from unwanted effects. This groundbreaking work aims to make once-fictional concepts a reality, changing our approach to health care.

Recent advancements at the intersection of nucleic acid nanotechnology and immunology have opened new avenues for therapeutic interventions. Interdisciplinary collaborative team, led by Dr. Kirill Afonin and including Laura Rebolledo, Dr. Weina Ke, Krishna Majithia, and Dr. Brittany Johnson from the University of North Carolina at Charlotte, Dr. Marina Dobrovolskaia and Edward Cedrone from the Nanotechnology Characterization Laboratory, Frederick National Laboratory for Cancer Research, as well as Dr. Jian Wang and Dr. Nikolay Dokholyan from Penn State University, have made a groundbreaking discovery in the modulation of immunostimulatory properties of nucleic acid nanoparticles (NANPs). Published in the esteemed journal ACS Applied Materials & Interfaces, their innovative research has found a way to mitigate the immune system’s response to these particles.

Dr. Afonin explains the core of their discovery: “By integrating specific DNA aptamers into the structures of NANPs, we observed regulated immune responses through cytokine production measurements. This capability could be harnessed to mitigate potential inflammation caused by nanomedicines.” This innovative approach not only promises safer nanomedicine applications but also opens new doors for utilizing NANPs in various therapeutic areas.

To achieve their findings, the team embarked on a detailed experimental process. They began by constructing the library of NANPs, incorporating different aptamers into their structure. This was done with the goal of observing the immune system’s response to these modified particles. “The experiments were designed comprehensively, encompassing varying numbers of aptamers embedded in different locations within NANPs and observing their effects on the immune responses” explains Laura Rebolledo, the first-name author of this work. Through this process, the team was able to identify specific compositions that were effective in reducing the immune system’s activation.

“The research underscores the significance of the structure-activity relationship in NANP design. Our study showcases the potential of ‘soft’ biodegradable NANPs, engineered with structural precision, to evade immune detection while retaining their intended functionalities more effectively.” Dr. Afonin notes. This insight is pivotal for developing NANPs that can be used safely in humans without eliciting unwanted immune reactions.

On the implications of their findings, Dr. Afonin shares, “Understanding the mechanistic insights into how NANPs interact with the immune system allows us to fine-tune the immune response for better therapeutic outcomes.” This advancement marks a significant step forward in the field of immunotherapy and vaccine development, offering new strategies for creating more effective and safer treatments. The closing insights of this pioneering study underline the significant potential of fibrous NANPs in biomedical applications, as discovered by Dr. Kirill Afonin and his team. Their work on aptamer-based modifications of NANPs sets the stage for safer nanomedicine and highlights innovative immunomodulation strategies. This leap forward by Dr. Afonin and colleagues marks a notable advancement in utilizing the immune system for therapeutic benefits, heralding new immunotherapy and vaccine development pathways that could transform patient care globally.


Rebolledo LP, Ke W, Cedrone E, Wang J, Majithia K, Johnson MB, Dokholyan NV, Dobrovolskaia MA, Afonin KA. Immunostimulation of Fibrous Nucleic Acid Nanoparticles Can be Modulated through Aptamer-Based Functional Moieties: Unveiling the Structure–Activity Relationship and Mechanistic Insights.  ACS Applied Materials and Interfaces, 16, 7, 8430–8441 2024.  PMID: 38344840; DOI: