NanoBiomaterials for Targeted Therapies
Our aim is to develop "smart" biomaterials, designed at the nanoscale with controlled architectures and functionalities, to provide in situ and in a targeted manner the required signals to promote nervous tissue repair and restoration of function.
- design of biomaterials at the nanoscale to induce specific cellular/tissue responses;
- evaluate in vitro and in vivo the biological performance of the developed nanobiomaterials.
Novel neuron targeted nanoparticles (NP) based on chitosan to deliver nucleic acids (NA) have been proposed and tested in vitro and in vivo. BDNF gene delivery mediated by the proposed nanosystems was found to be neuroprotective in peripheral nerve injury. The proposed NPs are highly versatile and transposable to other cell/tissues. As a proof, a collaboration was established in the design of NPs for NA delivery to the stomach in the treatment of gastric cancer.
Imaging flow cytometry, AFM and microfluidic platforms have also been proposed as new strategies to test NP bioperformance.
New hybrid-biodegradable, biocompatible, non-toxic, and water-soluble PEG–GATGE dendritic block copolymers have been proposed as novel degradable dendrimers for efficient and targeted nucleic acid delivery with the aim of neuroprotection and neurorepair of the ischemic brain.
We established a fibrin hydrogel platform with stiffness matching that of the human brain capable to support the survival, proliferation, and neuronal differentiation of single murine/human ES-derived neural stem/progenitor cells, envisaging its use for delivery of neural progenitors into the CNS. Fibrin functionalization with cell adhesive motifs binding to α6β1 integrin receptors further enhanced NSC neurite outgrowth and led to improved functional recovery after implantation in a SCI model.
A simple and reproducible 3D tissue engineered culture system of astrogliosis has been built, which mimics many features of the glial scar that is being explored in CNS drug screenings and remyelination strategies.
Ongoing projects are funded by FCT, INFARMED, H2020 ITN mCBEEs (www.mcbees.eu) and Santa Casa da Misericórdia de Lisboa and do Porto.
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An affinity-based approach to engineer laminin-presenting cell instructive microenvironments. Biomaterials192:601-611, 2019. [Journal: Article] [CI: 3] [IF: 10,3]
DOI: 10.1016/j.biomaterials.2018.10.039 SCOPUS: 85059918479. .
Moreno P.M.D., Ferreira A.R., Salvador D., Rodrigues M.T., Torrado M., Carvalho E.D., Tedebark U., Sousa M.M., Amaral I.F., Wengel J., Pêgo A.P.,
Hydrogel-Assisted Antisense LNA Gapmer Delivery for In Situ Gene Silencing in Spinal Cord Injury. Molecular Therapy - Nucleic Acids11:393-406, 2018. [Journal: Article] [CI: 11] [IF: 5,9]
DOI: 10.1016/j.omtn.2018.03.009 SCOPUS: 85045213607. .
Santos S.D., Xavier M., Leite D.M., Moreira D.A., Custódio B., Torrado M., Castro R., Leiro V., Rodrigues J., Tomás H., Pêgo A.P.,
PAMAM dendrimers: blood-brain barrier transport and neuronal uptake after focal brain ischemia. Journal of Controlled Release291:65-79, 2018. [Journal: Article] [CI: 14] [IF: 7,9]
DOI: 10.1016/j.jconrel.2018.10.006 SCOPUS: 85055160262. .
Silva J., Bento A.R., Barros D., Laundos T.L., Sousa S.R., Quelhas P., Sousa M.M., Pêgo A.P., Amaral I.F.,
Fibrin functionalization with synthetic adhesive ligands interacting with a6ß1 integrin receptor enhance neurite outgrowth of embryonic stem cell-derived neural stem/progenitors. Acta Biomaterialia59:243-256, 2017. [Journal: Article] [CI: 8] [IF: 6,4]
DOI: 10.1016/j.actbio.2017.07.013 SCOPUS: 85023776762. .
Leiro V., Garcia J.P., Moreno P.M.D., Spencer A.P., Fernandez-Villamarin M., Riguera R., Fernandez-Megia E., Paula Pêgo A.,
Biodegradable PEG-dendritic block copolymers: Synthesis and biofunctionality assessment as vectors of siRNA. Journal of Materials Chemistry B5(25):4901-4917, 2017. [Journal: Article] [CI: 9] [IF: 4,8]
DOI: 10.1039/c7tb00279c SCOPUS: 85021637380. .
Gomes C.P., Lopes C.D.F., Leitner M., Ebner A., Hinterdorfer P., Pêgo A.P.,
Atomic Force Microscopy as a Tool to Assess the Specificity of Targeted Nanoparticles in Biological Models of High Complexity. Advanced Healthcare Materials6(21):, 2017. [Journal: Article] [CI: 4] [IF: 5,6]
DOI: 10.1002/adhm.201700597 SCOPUS: 85026363665. .
Lopes C.D.F., Gonçalves N.P., Gomes C.P., Saraiva M.J., Pêgo A.P.,
BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury. Biomaterials121:83-96, 2017. [Journal: Article] [CI: 32] [IF: 8,8]
DOI: 10.1016/j.biomaterials.2016.12.025 SCOPUS: 85008958194. .
Lopes C.D.F., Gomes C.P., Neto E., Sampaio P., Aguiar P., Pêgo A.P.,
Microfluidic-based platform to mimic the in vivo peripheral administration of neurotropic nanoparticles. Nanomedicine11(24):3205-3221, 2016. [Journal: Article] [CI: 6] [IF: 4,7]
DOI: 10.2217/nnm-2016-0247 SCOPUS: 84998705753. .
Pires L.R., Guarino V., Oliveira M.J., Ribeiro C.C., Barbosa M.A., Ambrosio L., Pêgo A.P.,
Ibuprofen-loaded poly(trimethylene carbonate-co-e-caprolactone) electrospun fibres for nerve regeneration. Journal of Tissue Engineering and Regenerative Medicine10(3):E154-E166, 2016. [Journal: Article] [CI: 31] [IF: 4]
DOI: 10.1002/term.1792 SCOPUS: 84961207080. .
Rocha D.N., Ferraz-Nogueira J.P., Barrias C.C., Relvas J.B., Pêgo A.P.,
Extracellular environment contribution to astrogliosislessons learned from a tissue engineered 3D model of the glial scar. Frontiers in Cellular Neuroscience9(SEPTEMBER):, 2015. [Journal: Article] [CI: 13] [IF: 4,6]
DOI: 10.3389/fncel.2015.00377 SCOPUS: 84944455274. .
Rocha D.N., Brites P., Fonseca C., Pêgo A.P.,
Poly(trimethylene carbonate-co-e-caprolactone) promotes axonal growth. PLoS ONE9(2):, 2014. [Journal: Article] [CI: 17] [IF: 3,2]
DOI: 10.1371/journal.pone.0088593 SCOPUS: 84896121626. .