This breakthrough has the potential to transform the field of biologics, particularly in the treatment of diseases where targeted drug delivery is critical. The new technique, published in ACS Central Science, showcases a novel approach to overcoming one of the most persistent challenges in drug development: safely and effectively delivering large protein-based therapeutics into cells.
Proteins, though highly effective as therapeutic agents, often face significant barriers when it comes to cellular delivery. Unlike small molecules, proteins are large and complex, making it difficult for them to pass through cellular membranes. This limitation has historically impeded the use of proteins in treating diseases at the cellular level, despite their potential to offer more specific and less toxic therapeutic effects.
The research, led by doctoral student Azmain Alamgir, under the mentorship of Professors Chris Alabi and Matt DeLisa, introduces a solution to this challenge by utilizing lipid nanoparticles, tiny bubbles of fat, to transport the cloaked proteins into cells. Lipid nanoparticles are not new to the world of drug delivery—they played a crucial role in the success of mRNA COVID-19 vaccines by Pfizer-BioNTech and Moderna. However, the innovation here lies in adapting this technology to carry proteins rather than nucleic acids.
The process works by "cloaking" the proteins with a negatively charged ion. This negative charge allows the proteins to interact with positively charged lipids, forming nanoparticles that can efficiently ferry the proteins into cells. Once inside, the proteins uncloak, becoming active and exerting their therapeutic effects where needed. This method was successfully demonstrated using ribonuclease A, which killed cancer cells, and monoclonal antibodies, which inhibited tumor signaling.
“The crux of our strategy is conceptually very simple,” said Alamgir. “We’re taking proteins and specifically remodeling their surfaces with negative charges so they look like nucleic acids and can similarly assemble into nanoparticles when formulated with characteristic lipids.”
The implications of this technology are vast. Protein-based therapeutics have long been prized for their ability to target specific biological pathways with high precision and low toxicity. However, their application has been limited by delivery challenges. By overcoming this hurdle, Cornell’s new cloaking method could enable a broader range of protein-based drugs to be developed and deployed, leading to more effective treatments for conditions like cancer, autoimmune diseases, and neurodegenerative disorders.
Moreover, the versatility of this approach suggests it could be adapted for other therapeutic proteins, potentially expanding its use across multiple areas of medicine. The researchers believe that with further development, this method could move from lab-based success to clinical application, offering a new frontier in the treatment of complex diseases.
As the global market for biologics continues to grow, innovations like this one from Cornell are crucial in ensuring that the full potential of protein-based therapies can be realized. This cloaking technique not only represents a significant scientific advancement but also holds promise for improving the lives of patients with conditions that are currently difficult to treat.
