Polypeptide-based nanomedicines: enhancing tropism and overcoming biological barriers

Place: Conference Room, IMDEA Nanociencia

Abstract: 

Polypeptides are already pivotal in various critical areas, notably nanomedicine1. The intricate interplay of multiple structural factors defines the physicochemical parameters and biological performance of polypeptide-conjugates, underscoring the necessity for detailed structure-activity relationship studies to refine hierarchical polypeptide conjugate design. Interestingly, structural complexity presents a unique opportunity, as even subtle structural modifications can confer exceptional and unforeseen biological performance1. 
In our research group, we have overcome classical limitations in polypeptide synthesis by employing precise controlled reactions, followed by thorough characterization to yield well-defined polypeptide architectures using NCA polymerization techniques2. Furthermore, post-polymerization techniques enable the introduction of diverse functionalities, resulting in a range of orthogonal reactive attachment sites1,3. Using these techniques and following a bottom-up strategy we have been able to obtain polypeptides with different architecture, including diblock-co-polymers or star-shaped with the capacity to self-assemble yielding supramolecular nanostructures. These structures exhibit intriguing properties related to tissue specificity4, subcellular compartment tropism5, and even the potential for brain delivery6. This strategy together with an adequate polymer-drug linker design4-7 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 node4, mitochondria5 or brain accumulation6.
The promising results obtained position these systems as potential nanocarriers for therapeutic and/or diagnostic applications8.

References

1.  a) T. Melnyk et al. Adv. Drug Deliv. Rev. 2020, 160, 136-169; b) Dordevic S. et al Drug Deliv. Trans. Res. 2021, 1-26
2. a) I Conejos-Sánchez et al Polym Chem 2013, 4, 3182- 318; b) Duro-Castaño, A., et al. Mol Pharm 2015, 12, 3639-3649; c) WO2017025298A1; d) WO2013060919 A1
3. a) M Barz et al. Polym. Chem. 2013, 4, 2980- 2994; b) S Dordevic et al Small 2023
4. a) A. Duro-Castaño, et al. Adv. Mat., 2017, 29, 1702888-n/a; b) L.I.F. Mura, A. Malfanti et al Adv Mat. 2025 DOI:10.1002/adma.202417348
5. a) C. Pegoraro et al Adv Drug Deliv Rev. 2024; b) Patent application EP23382668.4, 2023. c) C. Pegoraro et al Adv Mat. 2025, 2411595. DOI: 10.1002/adma.202411595 d) C. Pegoraro et al J Mat Chem B 2025, DOI: 10.1039/D4TB02434F
6. A. Duro-Castaño et al. Science Advances 2021; 7: eabf9180; b) Patent EP22383152.0, 2022
7. a) J.J. Arroyo-Crespo, et al. Biomaterials, 2018, 186, 8-21; b) J.J. Arroyo‐Crespo, et al. Adv. Func. Mat., 2018, 28(22), 1800931; c) P. Boix-Montesinos et al J. Control Rel. 2024
8. Conejos-Sánchez I., et al Current Opin. Biomed.l Eng. 2021, 20,100323

Short biography: 

Prof. María J. Vicent is the head of the Polymer Therapeutics Lab. at Príncipe Felipe Research Center (CIPF) since 2006 and coordinator of the Cancer Program. She is also responsible for the Screening Platform, a Specialist Site in the European infrastructure EU-OPENSCREEN. She serves as president-elect for the Controlled Release Society (CRS), Vice-president of the Chemical Biology group within the RSEQ and is editor in chief of Advanced Drug Delivery Reviews. Dr. Vicent's research group (http://www.VicentResearchLab.com), specializes in developing novel nanopharmaceuticals for therapeutic and diagnostic applications, particularly in addressing unmet clinical needs through Polymer Therapeutics. Her work has been supported by national and European grants, including prestigious awards like the ERC Consolidator grant-MyNano, ERCPoC-POLYMMUNE, ERCPoC-Polybraint, and Fund Health La Caixa-NanoPanTher, PINT, NanoGBA or NanoERT; received from both academia and industry. María has been honored with several awards, apart from the very recent award Jaume I in New technologies 2025, she also received the Samyang award and several Women in Science recognitions. Recognized for her contributions, Dr. Vicent is a member of the National Academy of Inventors (FNAI) and a fellow of the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows since 2019. She was also inducted into the Controlled Release Society (CRS) College of Fellows in 2021. María has co-authored around 160 peer-reviewed papers and holds 15 patents. Six of these patents have been licensed to the pharmaceutical industry, with one contributing to the founding of the spin-off company 'Polypeptide Therapeutic Solutions S.L.' in Valencia, Spain, established in 2012 and rebranded as Curapath after its acquisition by Arcline in 2021 now a well-known CDMO with 100 employees.

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