Novel Delivery of Cyclic-Diguanylate Monophosphate Utilizing Amyloid Depots
<b>Background:</b> Recently, cyclic diguanylate monophosphate (c-di-GMP) drug delivery has garnered interest due to its potential in cancer immune modulation. In this pilot study, we developed a novel c-di-GMP formulation based on peptide amyloids. The amyloid depots were formed by combi...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/5/668 |
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| Summary: | <b>Background:</b> Recently, cyclic diguanylate monophosphate (c-di-GMP) drug delivery has garnered interest due to its potential in cancer immune modulation. In this pilot study, we developed a novel c-di-GMP formulation based on peptide amyloids. The amyloid depots were formed by combining an amyloidogenic prone 12 amino acid peptide sequence of receptor-interacting protein kinase 3 (RIP3) with cationic lipid ALC-0315, or using lysozyme proteins. Both RIP3 and lysozyme proteins have intrinsic physiological functions. This is the first time intrinsic peptides/protein-based amyloids have been explored for c-di-GMP delivery. The main goal was to evaluate how these amyloid depots could enhance c-di-GMP drug delivery and modulate responses in RAW 264.7 macrophage-like cells. <b>Methods:</b> Physicochemical characterization and cellular assays were utilized to characterize the amyloid structures and assess the efficacy. <b>Results:</b> Our results show that amyloid aggregates significantly improve the therapeutic efficacy of c-di-GMP. When RAW 264.7 cells were treated with c-di-GMP amyloids, we observed at least a 1.5-fold change in IL-6 expression, nitric oxide (NO) production, and reactive oxygen species (ROS) production compared to treatment with 5x free c-di-GMP treatment, which suggests that this system holds promise for enhanced therapeutic effects. <b>Conclusions:</b> Overall, these findings emphasize the potential of amyloid-based delivery systems as a promising approach for c-di-GMP delivery, warranting further investigations into their potential in therapeutic applications. |
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| ISSN: | 1999-4923 |