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Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway
Anne V Yagolovich1,2, Marine E Gasparian1, Dmitry A Dolgikh1,2
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.
Abstract:
The TRAIL (TNF-related apoptosis-inducing ligand) apoptotic pathway is extensively exploited in the development of targeted antitumor therapy due to TRAIL specificity towards its cognate receptors, namely death receptors DR4 and DR5. Although therapies targeting the TRAIL pathway have encountered many obstacles in attempts at clinical implementation for cancer treatment, the unique features of the TRAIL signaling pathway continue to attract the attention of researchers. Special attention is paid to the design of novel nanoscaled delivery systems, primarily aimed at increasing the valency of the ligand for improved death receptor clustering that enhances apoptotic signaling. Optionally, complex nanoformulations can allow the encapsulation of several therapeutic molecules for a combined synergistic effect, for example, chemotherapeutic agents or photosensitizers. Scaffolds for the developed nanodelivery systems are fabricated by a wide range of conventional clinically approved materials and innovative ones, including metals, carbon, lipids, polymers, nanogels, protein nanocages, virus-based nanoparticles, dendrimers, DNA origami nanostructures, and their complex combinations. Most nanotherapeutics targeting the TRAIL pathway are aimed at tumor therapy and theranostics. However, given the wide spectrum of action of TRAIL due to its natural role in immune system homeostasis, other therapeutic areas are also involved, such as liver fibrosis, rheumatoid arthritis, Alzheimer's disease, and inflammatory diseases caused by bacterial infections. This review summarizes the recent innovative developments in the design of nanodelivery systems modified with TRAIL pathway-targeting ligands.
Insights
Novel nanodelivery systems targeting the TNF-related apoptosis-inducing ligand (TRAIL) pathway show promise for cancer therapy and other diseases. These systems enhance ligand valency for improved apoptosis signaling and can combine therapies for synergistic effects.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- The TNF-related apoptosis-inducing ligand (TRAIL) pathway is a key target for cancer therapy due to its specific induction of apoptosis in cancer cells via death receptors DR4 and DR5.
- Despite challenges in clinical application, TRAIL pathway research continues, focusing on enhancing its therapeutic efficacy.
Purpose of the Study:
- To review recent advancements in designing nanodelivery systems for TRAIL pathway targeting.
- To explore the potential of these nanodelivery systems in cancer therapy, theranostics, and other diseases like liver fibrosis and inflammatory conditions.
Main Methods:
- Design of novel nanoscaled delivery systems to increase TRAIL ligand valency for enhanced death receptor clustering and apoptosis signaling.
- Fabrication of nanodelivery scaffolds using diverse materials including metals, polymers, lipids, and DNA origami nanostructures.
- Development of complex nanoformulations for co-delivery of TRAIL ligands with other therapeutic agents like chemotherapeutics or photosensitizers.
Main Results:
- Nanodelivery systems significantly improve TRAIL-mediated apoptosis signaling by increasing ligand valency.
- Versatile nanoformulations enable synergistic therapeutic effects through combined treatments.
- Diverse materials and nanostructures are utilized for fabricating effective TRAIL-targeting nanotherapeutics.
Conclusions:
- Nanodelivery systems offer a promising strategy to overcome obstacles in TRAIL-based cancer therapy.
- TRAIL-targeting nanotherapeutics have potential applications beyond oncology, including autoimmune and degenerative diseases.
- Continued innovation in nanodelivery systems is crucial for realizing the full therapeutic potential of the TRAIL pathway.
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