Seminar

Versatile Crosslinked Star-shaped Polypeptide Conjugates with Controlled Self-assembly as Therapeutics

María Jesús Vicent, PhD

Polypeptides are already playing a major role on a number of different relevant areas such as nanomedicine [1]. 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 performance [2]. In their group, they 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 (including stars, graft and block-copolymers) by NCA polymerization techniques [3]. In addition, post-polymerization techniques allow them the introduction of a variety of functionalities yielding a set of orthogonal reactive attachment sides [4]. Using these techniques and following a bottom-up strategy they have been able to obtain star-based polypeptide architectures with the capacity to self-assemble yielding supramolecular nanostructures with interesting properties [5]. This strategy 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 accumulation [5]. These results allow them to envisage these systems as promising nanocarriers for therapeutic or diagnostic applications, especially in anti-cancer treatments. Additionally, further studies to identify the mechanism for the significant accumulation found in the lymph nodes will open up a wide range of opportunities for the currently unsuccessful clinical approaches to target lymph node metastasis, imaging of sentinel lymph node and cancer immunotherapy. Duro-Castano A., Conejos-Sánchez I., Vicent M.J. Polymers 2014, 6, 515-551. 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 Acknowledgments Spanish Ministry of Economy and Competitiveness (SAF2016-80427-R) and the European Research Council (Grant ERC-CoG-2014-648831 MyNano) 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).