Amaya Niño‐Pariente

Centro de Investigacion Principe Felipe

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Marı́a J. Vicent

Centro de Investigacion Principe Felipe

Vicent J. Nebot

Centro de Investigacion Principe Felipe

Ana Armiñán

Centro de Investigacion Principe Felipe

Alison Paul

Kerala Agricultural University

Aroa Duro‐Castaño

Centro de Investigacion Principe Felipe

Natàlia Feiner‐Gracia

Institute of Advanced Chemistry of Catalonia

Elena Gallon

Centro de Investigacion Principe Felipe

Lorenzo Albertazzi

Eindhoven University of Technology

Juan J. Arroyo‐Crespo

Centro de Investigacion Principe Felipe

Ibane Abasolo

Vall d'Hebron Institut de Recerca

Cooperative Institutions

Centro de Investigacion Principe Felipe

Instituto de Salud Carlos III

Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine

Vall d'Hebron Institut de Recerca

Universitat Autònoma de Barcelona

CIBBIM-Nanomedicine

University of Cambridge

Wellcome/MRC Cambridge Stem Cell Institute

Medical Research Council

Trinity College Dublin

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Capturing “Extraordinary” Soft‐Assembled Charge‐Like Polypeptides as a Strategy for Nanocarrier Design

Advanced Materials (2017)

Aroa Duro‐Castaño Vicent J. Nebot Amaya Niño‐Pariente Ana Armiñán Juan J. Arroyo‐Crespo

The rational design of nanomedicines is a challenging task given the complex architectures required for the construction of nanosized carriers with embedded therapeutic properties and the complex interface of these materials with the biological environment. Herein, an unexpected charge-like attraction mechanism of self-assembly for star-shaped polyglutamates in nonsalty aqueous solutions is identified, which matches the ubiquitous "ordinary-extraordinary" phenomenon previously described by physicists. For the first time, a bottom-up methodology for the stabilization of these nanosized soft-assembled star-shaped polyglutamates is also described, enabling the translation of theoretical research into nanomaterials with applicability within the drug-delivery field. Covalent capture of these labile assemblies provides access to unprecedented architectures to be used as nanocarriers. The enhanced in vitro and in vivo properties of these novel nanoconstructs as drug-delivery systems highlight the potential of this approach for tumor-localized as well as lymphotropic delivery.

Nanocarriers

Rational design

Nanomaterials

10.1002/adma.201702888

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Citations (47)

Design of Poly‐l‐Glutamate‐Based Complexes for pDNA Delivery

Macromolecular Bioscience (2017)

Amaya Niño‐Pariente Ana Armiñán Sören Reinhard Claudia Scholz Ernst Wagner

Abstract Due to the polyanionic nature of DNA, typically cationic or neutral delivery vehicles have been used for gene delivery. As a new approach, this study focuses on the design, development, and validation of nonviral polypeptide‐based carriers for oligonucleotide delivery based on a negatively charged poly‐ l ‐glutamic acid (PGA) backbone partly derivatized with oligoaminoamide residues. To this end, PGA‐derivatives modified with different pentameric succinyl tetraethylene pentamines (Stp 5 ) are designed. Optionally, histidines for modulation of endosomal buffer capacity and cysteines for pDNA complex stabilization are included, followed by characterization of biophysical properties and gene transfer efficiency in N2a neuroblastoma or 4T1 breast cancer cells. image

Cationic polymerization

Glutamic acid

10.1002/mabi.201700029

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Citations (11)

Relevant Physicochemical Descriptors of "Soft Nanomedicines" to Bypass Biological Barriers

Zenodo (CERN European Organization for Nuclear Research) (2015)

Amaya Niño‐Pariente Vicent J. Nebot Marı́a J. Vicent

10.5281/zenodo.804598

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Polyornithine-based polyplexes to boost effective gene silencing in CNS disorders

Nanoscale (2019)

Inmaculada Conejos‐Sánchez Elena Gallon Amaya Niño‐Pariente Jayden A. Smith Alerie Guzman de la Fuente

Novel biodegradable and biocompatible polyornithine derivatives as non-viral vectors for siRNA exhibit effectively silence gene expression in primary neural cells.

Silence

Biocompatible material

10.1039/c9nr06187h

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Citations (15)

Nanocarriers: Capturing “Extraordinary” Soft‐Assembled Charge‐Like Polypeptides as a Strategy for Nanocarrier Design (Adv. Mater. 39/2017)

Advanced Materials (2017)

Aroa Duro‐Castaño Vicent J. Nebot Amaya Niño‐Pariente Ana Armiñán Juan J. Arroyo‐Crespo

A novel strategy developed by Vicent J. Nebot, María J. Vicent, and co-workers in article number 1702888 to produce nanosized drug carriers may improve the anticancer drug activity of polymer therapeutics and patient treatment. The discovery of an attractive force between negatively charged star-shaped-polypeptides allows single stars to self-assemble into unprecedented larger spherical structures with enhanced pharmacokinetic characteristics. Furthermore, selective lymph-node accumulation of these carriers may lead to applications in anti-metastatic and immunotherapeutic strategies.

Nanocarriers

Star polymer

Star (game theory)

10.1002/adma.201770280

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Citations (2)

Relevant Physicochemical Descriptors of “Soft Nanomedicines” to Bypass Biological Barriers

Current Pharmaceutical Design (2016)

Amaya Niño‐Pariente Vicent J. Nebot Marı́a J. Vicent

Herein, we present an overview on the current status of the characterization techniques and methodologies used to study the physicochemical descriptors that influence the final clinical performance of a given nanomedicine. The described techniques were selected based on their suitability to operate under relevant “native” conditions that mimic the physiological environment. Special emphasis is placed on those techniques that hold a greater potential to unravel dynamic, structural, and compositional features of soft organic nanomedicines relevant to the ability to bypass biological barriers, and hence allow for the rational design of drug delivery platforms with improved biological output. Keywords: Nanomedicines, drug delivery systems, biological barriers, characterization techniques, polymer therapeutics.

10.2174/1381612822666151216152143

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In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal‐Based Paclitaxel Conjugate for Prostate Cancer Therapy

Advanced Healthcare Materials (2021)

Yolanda Fernández Julie Movellan Laia Foradada Vanessa Giménez Natalia García‐Aranda

Abstract Prostate cancer (PCa), one of the leading causes of cancer‐related deaths, currently lacks effective treatment for advanced‐stage disease. Paclitaxel (PTX) is a highly active chemotherapeutic drug and the first‐line treatment for PCa; however, conventional PTX formulation causes severe hypersensitivity reactions and limits PTX use at high concentrations. In the pursuit of high molecular weight, biodegradable, and pH‐responsive polymeric carriers, one conjugates PTX to a polyacetal‐based nanocarrier to yield a tert ‐Ser‐PTX polyacetal conjugate. tert ‐Ser‐PTX conjugate provides sustained release of PTX over 2 weeks in a pH‐responsive manner while also obtaining a degree of epimerization of PTX to 7‐epi‐PTX. Serum proteins stabilize tert ‐Ser‐PTX, with enhanced stability in human serum versus PBS (pH 7.4). In vitro efficacy assessments in PCa cells demonstrate IC 50 values above those for the free form of PTX due to the differential cell trafficking modes; however, in vivo tolerability assays demonstrate that tert ‐Ser‐PTX significantly reduces the systemic toxicities associated with free PTX treatment. tert ‐Ser‐PTX also effectively inhibits primary tumor growth and hematologic, lymphatic, and coelomic dissemination, as confirmed by in vivo and ex vivo bioluminescence imaging and histopathological evaluations in mice carrying orthotopic LNCaP tumors. Overall, the results suggest the application of tert ‐Ser‐PTX as a robust antitumor/antimetastatic treatment for PCa.

Nanocarriers

Ex vivo

10.1002/adhm.202101544

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Citations (18)