Supramolecular functionalizable linear–dendritic block copolymers for the preparation of nanocarriers by microfluidics

Abad, Miriam (Universidad de Zaragoza) ; Martínez-Bueno, Alejandro ; Mendoza, Gracia ; Arruebo, Manuel (Universidad de Zaragoza) ; Oriol, Luis (Universidad de Zaragoza) ; Sebastián, Víctor (Universidad de Zaragoza) ; Piñol, Milagros (Universidad de Zaragoza)

Resumen: Hybrid linear–dendritic block copolymers (LDBCs) having dendrons with a precise number of peripheral groups that are able to supramolecular bind functional moieties are challenging materials as versatile polymeric platforms for the preparation of functional polymeric nanocarriers. PEG2k-b-dxDAP LDBCs that are based on polyethylene glycol (PEG) as hydrophilic blocks and dendrons derived from bis-MPA having 2, 6-diacylaminopyridine (DAP) units have been efficiently synthesized by the click coupling of preformed blocks, as was demonstrated by spectroscopic techniques and mass spectrometry. Self-assembly ability was first checked by nanoprecipitation. A re-producible and fast synthesis of aggregates was accomplished by microfluidics optimizing the total flow rate and phase ratio to achieve spherical micelles and/or vesicles depending on dendron generation and experimental parameters. The morphology and size of the self-assemblies were studied by TEM, Cryogenic Transmission Electron Microscopy (cryo-TEM), and Dynamic Light Scattering (DLS). The cytotoxicity of aggregates synthesized by microfluidics and the influence on apoptosis and cell cycle evaluation was studied on four cell lines. The self-assemblies are not cytotoxic at doses below 0.4 mg mL–1. Supramolecular functionalization using thymine derivatives was explored for reversibly cross-linking the hydrophobic blocks. The results open new possibilities for their use as drug nanocarriers with a dynamic cross-linking to improve nanocarrier stability but without hindering disassembly to release molecular cargoes.

Idioma: Inglés

DOI: 10.3390/polym13050684

Año: 2021

Publicado en: Polymers 13, 5 (2021), 684 [27 pp.]
ISSN: 2073-4360

Factor impacto JCR: 4.967 (2021)

Categ. JCR: POLYMER SCIENCE rank: 16 / 90 = 0.178 (2021) - Q1 - T1

Factor impacto CITESCORE: 5.7 - Materials Science (Q1)

Factor impacto SCIMAGO: 0.726 - Polymers and Plastics (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/E47-17R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-IIS/MS19-00092
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-099019-A-I00
Financiación: info:eu-repo/grantAgreement/ES/MINECO/MAT2017-84838-P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)