Explore groundbreaking nanomedicine innovations with DIVERSA. Learn how advanced gene therapies are overcoming liver tropism, unlocking new potential in targeted treatments for oncology, neurology, and more.
Expanding Horizons in Nanomedicine: Overcoming Liver Tropism with Advanced Non-Viral Vectors
In the dynamic landscape of modern medicine, the development of non-viral vectors has emerged as a groundbreaking innovation in gene therapy and nanomedicine. A recent comprehensive review published in Nature Nanotechnology (Link to Article) talks about the latest advancements in this field, focusing on strategies to overcome the natural tendency of nanoparticles to accumulate in the liver—a phenomenon known as liver tropism. This review is particularly relevant for companies like DIVERSA, which are at the forefront of developing cutting-edge drug delivery systems for therapeutic agents.
The Success Story of Nanomedicine despite Liver Tropism
Nanotechnology has made big strides in the medical field, with numerous groundbreaking innovations already entering clinical practice. One of the most important successes is the development and use of lipid nanoparticles (LNPs), which have been very useful in the delivery of mRNA vaccines, particularly during the COVID-19 pandemic. These nanoparticles have been optimized to deliver their cargo effectively, leading to the rapid development and global use of mRNA vaccines such as Comirnaty® (Pfizer-BioNTech) and Spikevax® (Moderna). This achievement shows the power of nanotechnology in addressing urgent public health needs and demonstrates the potential of nanoparticles in therapeutic applications beyond traditional medicines.
The success of nanomedicine is not limited to vaccines. To date, approximately 60 nanomedicine products have been approved by the FDA and EMA, impacting various therapeutic areas, and many more are currently under clinical development to make significant impacts in treating several diseases. Somes well-known examples are:
- Doxil® (Doxorubicin HCl Liposome Injection): A liposomal formulation of doxorubicin used to treat ovarian cancer, multiple myeloma, and Kaposi’s sarcoma. The liposomal encapsulation improves drug delivery and reduces cardiotoxicity.
- Abraxane® (Paclitaxel Protein-Bound Particles for Injectable Suspension): A nanoparticle albumin-bound formulation of paclitaxel used in the treatment of breast cancer, non-small cell lung cancer, and pancreatic cancer. It enhances the delivery of paclitaxel to tumors while reducing side effects.
- Onivyde® (Irinotecan Liposome Injection): A liposomal formulation of irinotecan approved for metastatic pancreatic cancer, improving drug efficacy and reducing systemic toxicity.
- Vyxeos® (Daunorubicin and Cytarabine Liposome Injection): Approved for the treatment of certain types of acute myeloid leukemia (AML), this liposomal formulation allows for the co-delivery of two chemotherapeutic agents, enhancing therapeutic outcomes.
The propensity of nanoparticles to accumulate in the liver has long been a double-edged sword. On one side, this liver tropism has been used to treat liver-specific diseases such as hepatitis, liver fibrosis, and hepatocellular carcinoma. On another, it has limited the broader use of nanoparticles to treat diseases in other organs. However, researchers have made significant progress in overcoming these challenges.
A key development is the design of surface-modified nanoparticles that can escape the liver’s capture and target other organs. These advancements include the use of polyethylene glycol (PEG) and other hydrophilic and polymeric coatings, which reduce protein adsorption and clearance by the liver. Similarly, the development of surface-decorated nanoparticles or functionalized nanoparticles with targeting ligands to direct them to specific cell types or tissues outside the liver, is a well-known strategy that has shown promising results and integrates the latest advances in molecular biology and other disciplines. These innovations are crucial to expand the reach of nanomedicine to treat diseases in other organs.
Efforts have also been made to enhance the stability and circulation time of nanoparticles in the bloodstream. By improving the pharmacokinetic profiles of these particles, researchers are developing nanoparticles that can circulate longer, penetrate deeper into tissues, and maintain their therapeutic efficacy over longer periods. This is especially important in the treatment of chronic diseases, where sustained drug release and prolonged therapeutic effects are critical.
The use of nanoparticles in cancer therapy has been another area of big success. Nanoparticles have been engineered to deliver chemotherapeutic agents directly to tumor sites, minimizing toxicity in the rest of the body and improving therapeutic efficacy. This approach is particularly important in treating metastatic cancers, where the liver is often a common site of metastasis. The ability of nanoparticles to accumulate in the liver can be used to target metastatic tumors, turning a potential limitation into a therapeutic advantage.
Despite the challenges associated with liver tropism, the success of nanotechnology in medicine is undeniable. The strategic modifications to nanoparticles have not only mitigated these challenges but have also opened new therapeutic avenues, making it possible to target diseases that were previously difficult to treat. As nanomedicine continues to evolve, the lessons learned from these successes will inform the development of the next generation of nanoparticles with even greater precision and efficacy.
Strategies and Innovations in Nanoparticle Delivery
Non-viral vectors, especially nanoparticles, have revolutionized the pharmaceutical industry. However, as discussed here, their clinical use has been mostly of application to liver-targeted therapies. The liver’s unique structure and role make it a primary target for nanoparticle accumulation, posing significant challenges when targeting other organs.
To address these challenges, researchers are investigating different strategies to modify the physicochemical properties of nanoparticles, aiming to reduce their liver accumulation and improve their distribution to other tissues. These strategies include altering the particle size, surface charge, and composition, and using targeting ligands that can guide nanoparticles to specific organs. By modifying these properties, nanoparticles can be designed to avoid the liver and reach other organs, broadening the scope of nanomedicine
The Broader Impact and Future Perspectives
The implications of these advancements in nanotechnology are far-reaching. Beyond addressing liver tropism, the field is moving towards the development of multifunctional nanoparticles that can target multiple organs, deliver a combination of therapeutic agents, and provide real-time monitoring of treatment efficacy. These next-generation nanoparticles could revolutionize the treatment of complex diseases, where a multi-faceted approach is often needed.
Moreover, the growing understanding of the interaction between nanoparticles and the body’s immune system opens up new possibilities for designing immune-modulatory therapies. By selectively targeting immune cells or modulating immune responses in specific tissues, nanoparticles could play a crucial role in treating autoimmune diseases, inflammatory conditions, and even in cancer immunotherapy.
DIVERSA continues to Innovate and Integrate these Scientific Advancements for the Development of Drug Delivery Formulations and Targeted Therapies
The field of nanomedicine is evolving rapidly, with significant progress being made in overcoming the barriers to effective non-viral vector delivery beyond the liver. Nanotechnology has already proven its clinical value, with liver-targeted therapies providing critical treatments for diseases such as liver cancer and viral hepatitis. This mix of cutting-edge research and practical application marks a new chapter in nanomedicine, one where the limitations of the past become the steppingstones for future breakthroughs. As we continue to understand and manipulate the behavior of nanoparticles within the human body, the potential for more advanced, effective, and widespread clinical applications grows exponentially, promising a healthier future for all.
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References
- Formenti, C., & Dalli, J. (2023). Strategies for non-viral vectors targeting organs beyond the liver. Nature Nanotechnology. doi.org/10.1038/s41565-023-01563-4
- Cullis, P. R., & Hope, M. J. (2017). Lipid nanoparticle systems for enabling gene therapies. Molecular Therapy, 25(7), 1467-1475. doi.org/10.1016/j.ymthe.2017.03.013
- Saber, N., Estape Senti, M., & Schiffelers, R. M. (2024). Lipid nanoparticles for nucleic acid delivery beyond the liver. Human Gene Therapy, (ja). doi.org/10.1089/hum.2024.106
- Mitragotri, S., Burke, P. A., & Langer, R. (2014). Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies. Nature Reviews Drug Discovery, 13(9), 655-672. doi.org/10.1038/nrd4363
- Seo, Y., Lim, H., Park, H., Yu, J., An, J., Yoo, H. Y., & Lee, T. (2023). Recent progress of lipid nanoparticles-based lipophilic drug delivery: focus on surface decorations. Pharmaceutics, 15(3), 772. doi.org/10.3390/pharmaceutics15030772
Links to Relevant Content:
- Nanoformulation: A leap forward in drug delivery: Learn more about our groundbreaking nanoformulation techniques that enhance drug delivery efficiency.
- Collaborative efforts in advancing healthcare: Discover how DIVERSA Technologies’ collaborations are pushing the boundaries of healthcare innovation.
- Targeted therapies in oncology: Explore our latest advancements in targeted therapies for oncology, offering new hope for cancer patients.
