Tumor Microenvironment and Targeted Therapies

João Nuno Moreira

João Nuno Moreira

PhD, Group Leader

Scientific activity is focused on the design of targeted entities, namely lipid- or polymeric-based nanosystems for drug and nucleic acid delivery, addressing the impact on the tumor microenvironment and cancer cells, both at the cellular and molecular level. This also involves the generation of novel antitumor strategies involving different gene therapy approaches, either per se or in combination with chemotherapeutic agents.

The main goals of the group point towards the identification and validation of target proteins overexpressed in tumors associated with clear unmet medical needs, combined with the demonstration of their importance for the tumorigenic process. We believe that this strategy will enable to establish the mechanism of action of the targeted strategies the members of the group have been working on, either with single or drug combinations. It will ultimately overcome the challenges posed by drug resistance and metastasis, thus leading to decrease of overall tumor burden and relapse as well, clearly benefiting cancer patients.

To further support the achievement of the referred scientific goals, and increase the translational potential of the generated knowledge, the involvement of researchers from hospitals and clinicians will be fostered from the early stages of the projects. This will be crucial to support the identified target proteins as markers for drug targeting, namely in patients-derived samples.

Group Members

Group Members

Group members are: João Nuno Moreira (PhD, Group Leader), Albina Bushmalyova (MSc Student), Alexandro Azevedo (MSc Student), Ana Filipa Cruz, Ana Rita Ribeiro, Anália Carmo (PhD), Daniel Oliveira (MSc Student), Daniela Santo (PhD Student), Dina Farinha (PhD Student), Gilberto Serrano de Almeida (PhD, Collaborator), Henrique Faneca (PhD), Mariangela Natale, Mariana Biscaia, Marta Pereira, Nuno Fonseca (PhD), Rita Martins (MSc Student), Rita Oliveira (PhD), Rose Cordeiro (PhD), Simaura Henriques (MSc Student), Teresa Abreu, Teresa Martins (PhD), Sérgio Simões (PhD).

Selected Publications

Abreu, T. R., Fonseca, N. A., Gonçalves, N., & Moreira, J. N. (2020). Current challenges and emerging opportunities of CAR-T cell therapies. J Control Release, 319, 246–261. https://doi.org/10.1016/j.jconrel.2019.12.047.

Fonseca, N. A., Gomes-da-Silva, L. C., Moura, V., Simoes, S., & Moreira, J. N. (2014). Simultaneous active intracellular delivery of doxorubicin and C6-ceramide shifts the additive/antagonistic drug interaction of non-encapsulated combination. J Control Release, 196, 122–131. https://doi.org/10.1016/j.jconrel.2014.09.024.

Fonseca, N. A., Gregorio, A. C., Valerio-Fernandes, A., Simoes, S., & Moreira, J. N. (2014). Bridging cancer biology and the patients’ needs with nanotechnology-based approaches. Cancer Treat Rev, 40(5), 626–635. https://doi.org/10.1016/j.ctrv.2014.02.002.

Fonseca, N. A., Rodrigues, A. S., Rodrigues-Santos, P., Alves, V., Gregorio, A. C., Valerio-Fernandes, A., Gomes-da-Silva, L. C., Rosa, M. S., Moura, V., Ramalho-Santos, J., Simoes, S., & Moreira, J. N. (2015). Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination. Biomaterials, 69, 76–88. https://doi.org/10.1016/j.biomaterials.2015.08.007.

Gomes-da-Silva, L. C., Fernandez, Y., Abasolo, I., Schwartz, S., Jr., Ramalho, J. S., Pedroso de Lima, M. C., Simoes, S., & Moreira, J. N. (2013). Efficient intracellular delivery of siRNA with a safe multitargeted lipid-based nanoplatform. Nanomedicine (Lond), 8(9), 1397–1413. https://doi.org/10.2217/nnm.12.174.

Gomes-da-Silva, L. C., Fonseca, N. A., Moura, V., Pedroso de Lima, M. C., Simões, S., & Moreira, J. N. (2012). Lipid-based nanoparticles for siRNA delivery in cancer therapy: Paradigms and challenges. Acc. Chem. Res., 45(7), 1163–1171. https://doi.org/10.1021/ar300048p.

Gregorio, A. C., Fonseca, N. A., Moura, V., Lacerda, M., Figueiredo, P., Simoes, S., Dias, S., & Moreira, J. N. (2016). Inoculated Cell Density as a Determinant Factor of the Growth Dynamics and Metastatic Efficiency of a Breast Cancer Murine Model. PLoS One, 11(11), e0165817. https://doi.org/10.1371/journal.pone.0165817.

Moura, V., Lacerda, M., Figueiredo, P., Corvo, M. L., Cruz, M. E., Soares, R., de Lima, M. C., Simões, S., & Moreira, J. N. (2012). Targeted and intracellular triggered delivery of therapeutics to cancer cells and the tumor microenvironment: Impact on the treatment of breast cancer. Breast Cancer Res. Treat., 133(1), 61–73. https://doi.org/10.1007/s10549-011-1688-7.

Romano, S., Moura, V., Simoes, S., Moreira, J. N.*, & Goncalves, J.* (2018). Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies. Sci Rep, 8(1), 7450. https://doi.org/10.1038/s41598-018-25816-8. *Corresponding authors.

Romano, Sofia, Fonseca, N., Simões, S., Gonçalves, J., & Moreira, J. N. (2019). Nucleolin-based targeting strategies for cancer therapy: From targeted drug delivery to cytotoxic ligands. Drug Discovery Today, 24(10), 1985–2001. https://doi.org/10.1016/j.drudis.2019.06.018.

Carvalho AM, Cordeiro R, Faneca H (2020). Silica-based gene delivery systems: from design to therapeutic applications. Pharmaceutics,12,649. https://doi:10.3390/pharmaceutics12070649

Vaz-Ramos, J., Cordeiro, R., Castro, M. M., Geraldes, C. F., Costa, B., Faneca, H., Durães, L. (2020). Supercritically dried superparamagnetic mesoporous silica nanoparticles for cancer theranostics. Material Science & Engineering C, 115:111124-111138.https://doi.org/10.1016/j.msec.2020.111124

Cordeiro, R. A., Serra, A., Coelho, J. F. J., & Faneca, H. (2019). Poly(β-amino ester)-based gene delivery systems: From discovery to therapeutic applications. Journal of Controlled Release, 310, 155-187.https://doi.org/10.1016/j.jconrel.2019.08.024

Santo, D., Mendonça, P. V., Lima, M. S., Cordeiro, R. A., Cabanas, L., Serra, A., Coelho, J.F.J., & Faneca, H. (2019). Poly(ethylene glycol)-block-poly(2-aminoethyl methacrylate hydrochloride)-Based Polyplexes as Serum-Tolerant Nanosystems for Enhanced Gene Delivery. Molecular Pharmaceutics, 16(5), 2129-2141.https://doi: 10.1021/acs.molpharmaceut.9b00101

Cordeiro, R. A., Santo, D., Farinha, D., Serra, A., Faneca*, H., & Coelho*, J. F. J. (2017). High transfection efficiency promoted by tailor-made cationic tri-block copolymer-based nanoparticles. Acta Biomaterialia, 47, 113-123. https://doi.org/10.1016/j.actbio.2016.10.015 (*Corresponding authors)

Santo, D., Cordeiro, R. A., Sousa, A., Serra, A., Coelho, J. F. J., & Faneca, H. (2017). Combination of Poly[(2-dimethylamino)ethyl methacrylate] and Poly(β-amino ester) Results in a Strong and Synergistic Transfection Activity. Biomacromolecules, 18(10), 3331-3342. https://doi: 10.1021/acs.biomac.7b00983

Selected Projects

CANCEL STEM - Tackling CANcer STEM CELls: a challenge and an opportunity to advance in anti-cancer therapy. COMPETE2020. PI: João Nuno Moreira.

NanoDoxer: Towards a single therapy with a synergistic drug combination against triple negative breast cancer and neuroblastoma by nucleolin-mediated multicellular targeting. EURONANOMED II (ERANET). PI: João Nuno Moreira.

ODD4PEGASEMP: PEGASEMP™ as an orphan drug for the treatment of rare diseases - a curative therapy for mesothelioma. CENTRO2020. PI: João Nuno Moreira.

Development of an innovative nanosystem to mediate a combined and multi-target therapeutic strategy to hepatocellular carcinoma”. POCI-01-0145-FEDER-30916 (FCT - Foundation for Science and Technology); 2018-2021; PI: Henrique Faneca.

Development of an innovative targeted-nanoparticle formulation for combined gene therapy and chemotherapy application in hepatocellular carcinoma. IF/01007/2015 (FCT Investigator Program — Foundation for Science and Technology); 2017-2021; PI: Henrique Faneca.

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