Macrophage modulation by selective peptide-drug conjugates
Macrophages play important roles in defence mechanisms and homeostasis. They represent a heterogeneous cell population that ranges from M1 pro-inflammatory macrophages to M2 anti-inflammatory ones, with different macrophage phenotypes in between depending on the microenvironment. Macrophages are hig...
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| Formato: | tesis doctoral |
| Fecha de publicación: | 2024 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/418510 |
| Acesso em linha: | http://hdl.handle.net/10261/418510 |
| Access Level: | acceso abierto |
| Palavra-chave: | Peptides Pharmacology Macrophages http://metadata.un.org/sdg/9 http://metadata.un.org/sdg/11 http://metadata.un.org/sdg/12 http://metadata.un.org/sdg/17 http://metadata.un.org/sdg/3 Ensure healthy lives and promote well-being for all at all ages Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation Make cities and human settlements inclusive, safe, resilient and sustainable Ensure sustainable consumption and production patterns Strengthen the means of implementation and revitalize the Global Partnership for Sustainable Development |
| Resumo: | Macrophages play important roles in defence mechanisms and homeostasis. They represent a heterogeneous cell population that ranges from M1 pro-inflammatory macrophages to M2 anti-inflammatory ones, with different macrophage phenotypes in between depending on the microenvironment. Macrophages are highly plastic cells that can swing from one state to the other and their deregulation can give rise to disease and its progression. For instance, M2 macrophages promote tumour growth via immunosuppression and angiogenesis, while M1 macrophages provide anti-tumour properties. In Crohn’s disease (CD) prolonged M1 activation and altered M2 function can contribute to the onset and activity of the disease. Therefore, to control these diseases it is important to have the ability to modulate macrophage’s phenotype. CD206 is a macrophage mannose endocytic receptor that is found in M2 tumour-associated macrophages (TAMs) and M1 pro-inflammatory macrophages in Crohn’s disease. Here, we present MACTIDE, a highly selective CD206 binding peptide that can be coupled to different payloads, such as verteporfin (V) or dexamethasone (D), to selectively deliver the drug, reducing in this way potential side effects of untargeted delivery. In this research, we demonstrate the potential of MACTIDE as a carrier to specifically deliver payloads to CD206+ macrophages as well as verify the ability of MACTIDE coupled to verteporfin (MACTIDE-V) to shift M2-like bone marrow-derived macrophages (BMDM) to an M1 phenotype with enhanced phagocytosis. We also introduce MACTIDE coupled to dexamethasone (MACTIDE-D) as a potential candidate to target inflammatory macrophages. |
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