REVIEW article
Front. Med. Technol.
Sec. Nano-Based Drug Delivery
Volume 7 - 2025 | doi: 10.3389/fmedt.2025.1591119
Enhancing Nucleic Acid Delivery via Lipid Nanoparticles: Integrating Artificial Intelligence for Predictive Modeling in Formulation Design
Provisionally accepted
Amir Mokhammad1
Afrida Malik1
Anas Wheba1
Sumith Yesudasan1Oluwanifemi Olagunju1Sean X Gu2
Timur O Yarovinsky2
John Hwa2
E. Vincent S. Faustino2Juliane Nguyen3
Kagya Amoako1*- 1University of New Haven, West Haven, United States
- 2Yale University, New Haven, Connecticut, United States
- 3University of North Carolina at Charlotte, Charlotte, North Carolina, United States
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The advent of messenger RNA (mRNA) therapeutics has revolutionized medicine, with its potential underscored by rapid advancements during the COVID-19 pandemic. Despite its promise, nucleic acid delivery remains a formidable challenge due to enzymatic degradation, cellular uptake barriers, and endosomal trapping. Therapeutic lipid nanoparticles (LNPs), pioneered in the 1970s, have emerged as the gold standard for delivering mRNA and other nucleic acids, offering unparalleled advantages in stability, biocompatibility, and cellular targeting. This review explores the evolution and design of LNPs, focusing on their role in hematologic therapies and platelet transfection, where unique challenges arise due to platelets' anucleate nature. The paper systematically evaluates the composition of LNPs, highlighting the role of ionizable, cationic, and neutral lipids in optimizing delivery efficiency, stability, and immune response modulation. Strategies to overcome platelet transfection barriers, including tailored lipid compositions and particle engineering, are discussed alongside advances in artificial intelligence (AI) for predictive nanoparticle design. Furthermore, it examines various nucleic acid cargoes, including mRNA, siRNA, and miRNA, and their therapeutic potential in addressing platelet-related disorders and advancing personalized medicine. Finally, the review delves into emerging technologies and the integration of AI to overcome existing barriers in nucleic acid delivery. By fostering interdisciplinary collaboration, this work aims to catalyze discoveries in LNP-based therapeutics and transformative advancements in hematologic treatments.
Keywords: Nucleic acid delivery, Liposome nanoparticles, artificial intelligence, platelets, Transfection
Received: 10 Mar 2025; Accepted: 26 May 2025.
Copyright: © 2025 Mokhammad, Malik, Wheba, Yesudasan, Olagunju, Gu, Yarovinsky, Hwa, Faustino, Nguyen and Amoako. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kagya Amoako, University of New Haven, West Haven, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.