Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/88570
Título: | Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems |
Autor(es): | Rodrigues, Daniel Barreira Moreira, Helena R. Cerqueira, Mariana T. Marques, A. P. Castro, António G. Reis, R. L. Pirraco, Rogério P. |
Palavras-chave: | Cytotoxic T cells Gellan Gum Nanoparticles T cell stimulation |
Data: | Set-2022 |
Editora: | BioMed Central (BMC) |
Revista: | Biomaterials Research |
Citação: | Rodrigues D. B., Moreira H. R., Cerqueira M. T., Marques A. P., Castro A. G., Reis R. L., Pirraco R. P. Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems, Biomaterials Research, Vol. 26, pp. 48, doi:10.1186/s40824-022-00297-z, 2022 |
Resumo(s): | Background: T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efcacy and relatively weak side efects. Systems that optimize the stimulation of T cells to improve therapeutic efcacy are therefore in constant demand. A way to achieve this is through artifcial antigen presenting cells that are complexes between vehicles and key molecules that target relevant T cell subpopulations, eliciting antigenspecifc T cell priming. In such T cell activator systems, the vehicles chosen to deliver and present the key molecules to the targeted cell populations are of extreme importance. In this work, a new platform for the creation of T cell activator systems based on highly tailorable nanoparticles made from the natural polymer gellan gum (GG) was developed and validated. Methods: GG nanoparticles were produced by a water in oil emulsion procedure, and characterized by dynamic light scattering, high resolution scanning electronic microscopy and water uptake. Their biocompatibility with cultured cells was assessed by a metabolic activity assay. Surface functionalization was performed with anti-CD3/ CD28 antibodies via EDC/NHS or NeutrAvidin/Biotin linkage. Functionalized particles were tested for their capacity to stimulate CD4+ T cells and trigger T cell cytotoxic responses. Results: Nanoparticles were approximately 150 nm in size, with a stable structure and no detectable cytotoxicity. Water uptake originated a weight gain of up to 3200%. The functional antibodies did efciently bind to the nanoparticles, as confrmed by SDS-PAGE, which then targeted the desired CD4+ populations, as confrmed by confocal microscopy. The developed system presented a more sustained T cell activation over time when compared to commercial alternatives. Concurrently, the expression of higher levels of key cytotoxic pathway molecules granzyme B/perforin was induced, suggesting a greater cytotoxic potential for future application in adoptive cancer therapy. Conclusions: Our results show that GG nanoparticles were successfully used as a highly tailorable T cell activator system platform capable of T cell expansion and re-education. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/88570 |
DOI: | 10.1186/s40824-022-00297-z |
ISSN: | 1226-4601 |
e-ISSN: | 2055-7124 |
Versão da editora: | https://dx.doi.org/10.1186/s40824-022-00297-z |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | 3B’s - Artigos em revistas/Papers in scientific journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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20917-rodrigues-et-al-2022.pdf | 7,21 MB | Adobe PDF | Ver/Abrir |