Publicação
Smart extracellular vesicles for targeted therapy in breast cancer
| Resumo: | A central challenge in cancer nanomedicine is achieving selective drug delivery that directs therapeutic agents specifically to tumor cells while minimizing adverse effects on healthy tissues. Over the past decades, drug delivery systems have advanced considerably, with nanocarriers explored as promising vehicles to improve treatment outcomes. Among these, extracellular vesicles (EVs), which are lipid bilayer enclosed particles naturally secreted by cells during both physiological and pathological processes, have attracted great interest. Their inherent biocompatibility, low immunogenicity, and natural ability to transport biological material position them as strong candidates for clinical translation. Building on these properties, we sought to improve the tumor specificity of EVs for the treatment of triple negative breast cancer (TNBC), an aggressive subtype that currently lacks effective targeted therapies. To this end, we developed an in-house TNBC-specific peptide, termed 231-Pep, through phage display screening, and conjugated it to PEG-phospholipid micelles, which were subsequently integrated into cell-derived EVs. Comprehensive analyses demonstrated that the engineered EVs exhibited markedly improved recognition and uptake by TNBC cells both in vitro and in vivo compared with unmodified controls, confirming their selective targeting capability. Furthermore, we showed that these EVs could be loaded with a broad range of therapeutic molecules, including small interfering RNAs, microRNAs, and functional proteins, underlining their versatility as adaptable drug delivery vehicles. Collectively, these findings suggest that peptide guided engineering of EVs offers a promising strategy to achieve precise drug delivery in TNBC and may pave the way for personalized therapeutic approaches that could be extended to other difficult to treat cancers. |
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| Autores principais: | Ferreira, Débora |
| Outros Autores: | Gandarela, Leonor B.; Silva, Catarina; C. Novo, Inês; Sousa, Mariana Martins; Pereira, Ana; Sousa, Diana Andrade; Rodrigues, L. R. |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | outro |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | A central challenge in cancer nanomedicine is achieving selective drug delivery that directs therapeutic agents specifically to tumor cells while minimizing adverse effects on healthy tissues. Over the past decades, drug delivery systems have advanced considerably, with nanocarriers explored as promising vehicles to improve treatment outcomes. Among these, extracellular vesicles (EVs), which are lipid bilayer enclosed particles naturally secreted by cells during both physiological and pathological processes, have attracted great interest. Their inherent biocompatibility, low immunogenicity, and natural ability to transport biological material position them as strong candidates for clinical translation. Building on these properties, we sought to improve the tumor specificity of EVs for the treatment of triple negative breast cancer (TNBC), an aggressive subtype that currently lacks effective targeted therapies. To this end, we developed an in-house TNBC-specific peptide, termed 231-Pep, through phage display screening, and conjugated it to PEG-phospholipid micelles, which were subsequently integrated into cell-derived EVs. Comprehensive analyses demonstrated that the engineered EVs exhibited markedly improved recognition and uptake by TNBC cells both in vitro and in vivo compared with unmodified controls, confirming their selective targeting capability. Furthermore, we showed that these EVs could be loaded with a broad range of therapeutic molecules, including small interfering RNAs, microRNAs, and functional proteins, underlining their versatility as adaptable drug delivery vehicles. Collectively, these findings suggest that peptide guided engineering of EVs offers a promising strategy to achieve precise drug delivery in TNBC and may pave the way for personalized therapeutic approaches that could be extended to other difficult to treat cancers. |
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