Abstract:
Polypeptides are already playing a major role on a number of different relevant areas such as nanomedicine1. The physico-chemical parameters of a polypeptide-conjugate, and hence its biological performance, are defined by an intricate interplay of multiple structural factors. This highlights the need for detailed structure-activity relationship studies to develop the hierarchical strategies of polypeptide conjugate design. However, structural complexity also represents a unique opportunity, since small changes at the structural level might endow nanomedicines with outstanding and unexpected biological performance2.
In our group, we have overcome the main classical limitations for the synthesis of defined polypeptides using precise controlled reactions followed by an adequate characterization yielding to well-defined polypeptidic architectures by NCA polymerization techniques3. In addition, post-polymerization techniques allow us the introduction of a variety of functionalities yielding a set of orthogonal reactive attachment sides4. Using these techniques and following a bottom-up strategy we have been able to obtain star-based polypeptide architectures with the capacity to self-assemble yielding supramolecular nanostructures with interesting properties5. This strategy together with an adequate polymer-drug linker design6 enabled in vitro and in vivo evaluation, revealing a lack of toxicity, an enhanced in vitro cell internalization rate and significantly greater terminal and accumulation half-life in vivo together with a significant lymph node accumulation5. These results allow us to envisage these systems as promising nanocarriers for therapeutic or diagnostic applications, especially in anti-cancer treatments including lymph node metastasis and cancer immunotherapy. Proof of Concept for metastatic breast cancer6 and for immunotherapy design in melanoma will be also shown as well as the use of this self-assembled architectures in applications such as neurodegenerative disorders, spinal cord injury or acute kidney injury.
References:
- a) Duro-Castano A., Conejos-Sánchez I., Vicent M.J. Polymers 2014, 6, 515-551; b) Duro-Castaño A,Movellan J, Vicent MJ Biomater. Sci., 2015,3, 1321-1334
- Zagorodko O., Arroyo-Crespo, J.J., Nebot, V.J., and Vicent, M.J.Macromolecular Bioscience 2017, 17, 1600316-n/a.
- a) Duro-Castano A., England, R.M., Razola, D., Romero, E., Oteo-Vives, M., Morcillo, M.A., and Vicent, M.J. Molecular Pharmaceutics 2015, 12, 3639-3649; b) Conejos-Sánchez I. Duro-Castano, A., Birke, A., Barz, M., and Vicent, M.J. Polymer chemistry 2013, 4, 3182-3186.
- Barz M., Duro-Castano A., Vicent M.J. Polymer Chemistry 2013, 4, 2989-2994
- Duro-Casaño Nebot, V. J., Niño-Pariente, A., Armiñán, A., Arroyo-Crespo, J. J., Paul, A., Feiner-Gracia, N., Albertazzi, L. and Vicent, M. J. Advanced Materials 2017, doi. 10.1002/adma.201702888
- a) Arroyo-Crespo, J.J, Armiñán A., Charbonnier D:, Balzano-Nogueira L., Huertas-López F., Martí C., Tarazona S., Forteza J., Conesa A., Vicent M.J. Biomaterials 2018, 186, 8-21; b) Arroyo‐Crespo, J.J., Deladriere, C. et al. Adv. Func. Mat. 2018. 28(22): p. 1800931
Acknowledgements:
Spanish Ministry of Economy and Competitiveness (SAF2016-80427-R) and the European Research Council (Grant ERC-CoG-2014-648831 MyNano, Grant ERC-PoC-2018-825798 Polymmune) and AVI (project INNVAL10/19/047 and Marató TV3 for financial support. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with FEDER funds (PO FEDER of Comunitat Valenciana 2014-2020).
Bio:
Head of Polymer Therapeutics Lab. Coordinator of Advance Therapies Are. Prince Felipe Research Center (CIPF).
Group Website: http://www.VicentResearchLab.com and http://www.cipf.es
Dr. María J. Vicent received her Ph.D. (2001) in chemistry after her research on solid supports from the Univ.Jaume I (Castellon, Spain) after several scientific stays in Prof. Fréchet’s lab. at the University California (Berkeley, USA). María then moved into more biomedically-oriented research, initially with the Spanish company Instituto Biomar, and subsequently at the Centre for Polymer Therapeutics at the Univ.Cardiff (Wales, UK) with Prof. R. Duncan after receiving a Marie Curie Postdoctoral Fellowship in 2002. In 2004, María joined CIPF (Valencia, Spain) as a research associate through a Marie Curie Reintegration contract and was promoted to her current position as the head of the Polymer Therapeutics Lab. in 2006. María is currently responsible for the Screening Platform and coordinates the Advanced Therapies Program at the CIPF. Furthermore, she has been the coordinator of the Valencian Community Strategy on Innovative Medicines with the lab. becoming one of the Specialist Sites in the ERIC-EU-OPENSCREEN.
María’s research group focuses on the development of novel nanopharmaceuticals for different therapeutic and diagnostic applications - in particular the application of Polymer Therapeutics in unmet clinical needs. María has supervised ten Ph.D. students, with ten more ongoing, with many funded through various competitive grants. Her group is funded by both national and EU grants (i.e. ERC Consolidator grant-MyNano, ERC-PoC-Polymmune, Fund Health La Caixa-NanoPanTher). María has received several prizes, including the IVth and the IXth Idea Awards, and she has been elected as member of American Institute for Medical and Biological Engineering (AIMBE) College of Fellows Class of 2019. María has co-authored >110 peer-reviewed papers (h index: 37; >5000 citations) and 10 patents, 3 already licensed to industry and a fourth used as the foundation of the spin-off company ‘Polypeptide Therapeutic Solutions S.L. (PTS)’ (Valencia, Spain) in 2012. María was the President of the Spanish-Portuguese Chapter of the Controlled Release Society (SPLC-CRS) and the chairperson in key conferences in the nanomedicine field, such as the Int. Symp. on Polymer Therapeutics: From Lab. to Clinical Practice (Valencia, Spain) and the annual CRS meeting in 2019. María is also the executive editor of Adv. Drug Deliv Rev, the associate editor of NanoMedicine: NBM and DDTR, and a member of the editorial boards of key journal in the field including, J. Control Rel., Polymer Chemistry, Biomaterial Sciences, and Mol. Pharmaceutics.
Representative Publications
- J. Arroyo-Crespo et al. Characterization of Triple-Negative Breast Cancer Preclinical Models Provides Functional Evidence of Metastatic Progression. Int. J. Cancer 2019, 145(8), 2267-2281.
- J. Arroyo-Crespo et al. Tumor Microenvironment-Targeted poly-L-glutamic acid-based Combination Conjugate for Enhanced Triple Negative Breast Cancer Treatment. Biomaterials 2018, 186, 8-21
- Duro-Castaño et al. In Vivo Imaging of MMP-13 Activity Using A Specific Polymer-FRET Peptide Conjugate Detects Early Osteoarthritis And Inhibitor Efficacy. Adv. Funct. Mat. 2018, 28, p1802738
- J. Arroyo-Crespo et al. Anticancer Activity Driven by Drug Linker Modification in a Polyglutamic Acid-based Combination-drug Conjugate. Adv. Funct. Mat. 2018, 28(22): p. 1800931.
- Armiñán, et al. (2018) Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models. Biomaterials 162, 144.
- Duro-Castaño, et al. (2017) Capturing Extraordinary Soft-Assembled Charge-Like Polypeptides as a Strategy for Nanocarrier Design. Adv. Mat., 2017, 29(39): p. 1702888-n/a. Cover Page.
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