Tuning the drug multimodal release through a co-assembly strategy based on magnetic gels


Self-assembled short peptide-based gels are highly promising drug delivery systems. However, implementing a stimulus often requires screening different structures to obtain gels with suitable properties, and drugs might not be well encapsulated and/or cause undesirable effects on the gel's properties. To overcome this challenge, a new design approach is presented to modulate the release of doxorubicin as a model chemotherapeutic drug through the interplay of (di)phenylalanine-coated magnetic nanoparticles, PEGylated liposomes and doxorubicin co-assembly in dehydropeptide-based gels. The composites enable an enhancement of the gelation kinetics in a concentration-dependent manner, mainly through the use of PEGylated liposomes. The effect of the co-assembly of phenylalanine-coated nanoparticles with the hydrogel displays a concentration and size dependence. Finally, the integration of liposomes as doxorubicin storage units and of nanoparticles as composites that co-assemble with the gel matrix enables the tuneability of both passive and active doxorubicin release through a thermal, and a low-frequency alternating magnetic field-based trigger. In addition to the modulation of the gel properties, the functionalization with (di)phenylalanine improves the cytocompatibility of the nanoparticles. Hereby, this work paves a way for the development of peptide-based supramolecular systems for on-demand and controlled release of drugs.



subject category

Chemistry; Science & Technology - Other Topics; Materials Science; Physics


Veloso, SRS; Tiryaki, E; Spuch, C; Hilliou, L; Amorim, CO; Amaral, VS; Coutinho, PJG; Ferreira, PMT; Salgueirino, V; Correa-Duarte, MA; Castanheira, EMS

our authors


This work was funded by Ministerio de Economia y Competitividad de Espana (PID2020-113704RB-I00 and PID2020-119242RB-I00), Xunta de Galicia (Centro Singular de Investigacion de Galicia - Accreditation 2019-2022 ED431G 2019/06 and IN607A 2018/5 and project ED431C 2020-06,), and European Union (EU-ERDF Interreg V-A - Spain-Portugal 0245_IBEROS_1_E, 0712_ACUINANO_1_E, and 0624_2IQBIONEURO_6_E, and Interreg Atlantic Area NANOCULTURE 1.102.531), and the European Union H2020-MSCA-RISE-2019 PEPSA-MATE project, and by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UIDB/04650/2020), IPC (UID/CTM/50025/2020) and CQUM (UIDB/00686/2020). FCT, FEDER, PORTUGAL2020 and COMPETE2020 are also acknowledged for funding under research projects PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020) and PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015). S. R. S. Veloso acknowledges FCT for a PhD grant (SFRH/BD/144017/2019). Support from MAP-Fis Doctoral Programme is also acknowledged.

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