Supramolecular ultra-short dehydropeptide-based hydrogels as potential affordable nanocarriers

A library of Cbz-protected dehydrodipeptides was synthesised and evaluated as minimalist hydrogels. The molecular aggregation, self-assembly, gelation and biocompatibility were thoroughly studied through fluorescence spectroscopy, and the mechanical properties were assessed. The compounds that afforded hydrogels were evaluated as drug delivery systems for curcumin and doxorubicin using biomembrane models.UIDB/04650/2020; UIDB/00686/2020; PTDC/QUI-QFI/28020/2017; PTDC/QUI-QOR/29015/2017; SFRH/BD/144017/201

Supramolecular plasmonic magnetic gels for controlled drug delivery

In this work, two different magnetic/plasmonic nanoparticle architectures were developed, characterized and combined with a naproxen N-capped dehydropeptide-based hydrogel. Spectroscopic techniques and rheologic assays were used were used to assess the gel physicochemical properties, the incorporation of a model drug (curcumin), drug transport towards model membranes and controlled drug release

Implications of nanoparticles functionalization in supramolecular magnetogels for drug delivery

In this work, dehydropeptide gels were loaded with citrate- or lipid-stabilized nanoparticles to evaluate the effect over doxorubicin release. Particularly, the lipid-stabilized nanoparticles co-assembled with the hydrogel fibres forming lipid-fibre interface domains.Portugal2020, Compete2020, FEDER. SFRH/BD/144017/2019. PTDC/QUI-QFI/28020/2017. UIDB/04650/202

Development of supramolecular peptide-based magnetolipogels: towards on-demand drug delivery

Solid and aqueous magnetoliposomes were encapsulated in supramolecular naproxen N-capped dehydrodipeptide-based hydrogels. Fluorescence spectroscopy was used to assess the dynamics of magnetoliposomes during gelation through co-encapsulation of Nile Red and curcumin. The final localization environment of encapsulated molecules was demonstrated to be independent of the magnetoliposomes architecture and of the used hydrogel.Foundation for Science and Technology (FCT-Portugal) for Funding of CF-UM-UP (UIDB/04650/2020) and CQUM (UIDB/00686/2020) and research projects PTDC/QUI-QFI/28020/2017 and PTDC/QUIQOR/29015/2017. S.R.S.V. acknowledges FCT for a PhD grant (SFRH/BD/144017/2019)

Supramolecular magnetolipogels: a co-assembly strategy for on-demand drug release

In this work, magnetic liposomes, both solid and aqueous, were loaded with a model drug and combined with dehydropeptide-based hydrogels. The encapsulated drug distributed between hydrogel fibres and magnetoliposomes lipid bilayer, which was demonstrated to be independent of the magnetoliposome’s nanoarchitecture, resulting in an attenuated drug release from the magnetolipogels compared to hydrogels.UIDB/00686/2020. UIDB/04650/2020. SFRH/BD/144017/201

Dehydropeptide-based plasmonic lipogels as bionanosystems for controlled drug release

In this work, silica-coated gold nanoparticles and liposomes (storage units) were combined with dehydropeptide-based hydrogels as a proof-of-concept to afford peptide-based NIR light-responsive lipogels. Several liposomes compositions were assessed to study its influence on the final assembly properties. Gold nanospheres were used to assess the preparation method that enabled a closer proximity of the nanoparticles to the liposomes.Ministerio de Economía y Competitividad de España (PID2020-113704RB-I00), Xunta de Galicia (Centro Singular de Investigación de Galicia - Accreditation 2019-2022 ED431G 2019/06 and IN607A 2018/5), and European Union-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)

Bolaamphiphilic Bis-Dehydropeptide hydrogels as potential drug release systems

The self-assembly of nanometric structures from molecular building blocks is an effective way to make new functional materials for biological and technological applications. In this work, four symmetrical bolaamphiphiles based on dehydrodipeptides (phenylalanyldehydrophenylalanine and tyrosyldehydrophenylalanine) linked through phenyl or naphthyl linkers (terephthalic acid and 2,6-naphthalenedicarboxylic acid) were prepared, and their self-assembly properties were studied. The results showed that all compounds, with the exception of the bolaamphiphile of tyrosyldehydrophenylalanine and 2,6-naphthalene dicarboxylic acid, gave self-standing hydrogels with critical gelation concentrations of 0.3 wt % and 0.4 wt %, using a pH trigger. The self-assembly of these hydrogelators was investigated using STEM microscopy, which revealed a network of entangled fibers. According to rheology, the dehydrodipeptide bolaamphiphilic hydrogelators are viscoelastic materials with an elastic modulus G' that falls in the range of native tissue (0.37 kPa brain-4.5 kPa cartilage). In viability and proliferation studies, it was found that these compounds were non-toxic toward the human keratinocyte cell line, HaCaT. In sustained release assays, we studied the effects of the charge present on model drug compounds on the rate of cargo release from the hydrogel networks. Methylene blue (MB), methyl orange (MO), and ciprofloxacin were chosen as cationic, anionic, and overall neutral cargo, respectively. These studies have shown that the hydrogels provide a sustained release of methyl orange and ciprofloxacin, while methylene blue is retained by the hydrogel network.Portugal2020, Compete2020, FEDER. PTDC/QUI-QOR/29015/2017. UIDB/04650/2020. UIDB/50006/2020. UID/QUI/00686/2019. UID/CTM/50025/2019. SFRH/BD/144017/201

Magnetogels: prospects and main challenges in biomedical applications

Drug delivery nanosystems have been thriving in recent years as a promising application in therapeutics, seeking to solve the lack of specificity of conventional chemotherapy targeting and add further features such as enhanced magnetic resonance imaging, biosensing and hyperthermia. The combination of magnetic nanoparticles and hydrogels introduces a new generation of nanosystems, the magnetogels, which combine the advantages of both nanomaterials, apart from showing interesting properties unobtainable when both systems are separated. The presence of magnetic nanoparticles allows the control and targeting of the nanosystem to a specific location by an externally applied magnetic field gradient. Moreover, the application of an alternating magnetic field (AMF) not only allows therapy through hyperthermia, but also enhances drug delivery and chemotherapeutic desired effects, which combined with the hydrogel specificity, confer a high therapeutic efficiency. Therefore, the present review summarizes the magnetogels properties and critically discusses their current and recent biomedical applications, apart from an outlook on future goals and perspectives.This work was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UID/FIS/04650/2013) and CQUM (UID/QUI/00686/2016). S.R.S.V. acknowledges FCT for a research grant under UID/FIS/04650/2013 funding.info:eu-repo/semantics/publishedVersio

Oxidative precipitation synthesis of calcium-doped manganese ferrite nanoparticles for magnetic hyperthermia

Superparamagnetic nanoparticles are of high interest for therapeutic applications. In this work, nanoparticles of calcium-doped manganese ferrites (CaxMn1−xFe2O4) functionalized with citrate were synthesized through thermally assisted oxidative precipitation in aqueous media. The method provided well dispersed aqueous suspensions of nanoparticles through a one-pot synthesis, in which the temperature and Ca/Mn ratio were found to influence the particles microstructure and morphology. Consequently, changes were obtained in the optical and magnetic properties that were studied through UV-Vis absorption and SQUID, respectively. XRD and Raman spectroscopy studies were carried out to assess the microstructural changes associated with stoichiometry of the particles, and the stability in physiological pH was studied through DLS. The nanoparticles displayed high values of magnetization and heating efficiency for several alternating magnetic field conditions, compatible with biological applications. Hereby, the employed method provides a promising strategy for the development of particles with adequate properties for magnetic hyperthermia applications, such as drug delivery and cancer therapy.This work was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UIDB/04650/2020, UIDP/04650/2020), CQUM (UIDB/00686/2020), CICECO Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020) and by Ministerio de Economía y Competitividad de España (PID2020-113704RB-I00 and PID2020-119242RB-I00), Xunta de Galicia (Centro Singular de Investigación 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. S.R.S. (872233) Veloso acknowledges FCT for a PhD grant (SFRH/BD/144017/2019). Support from MAP-Fis Doctoral Programme is also acknowledged

Magnetoliposomes incorporated in peptide-based hydrogels: towards development of magnetolipogels

A major problem with magnetogels is the encapsulation of hydrophobic drugs. Magnetoliposomes not only provide these domains but also improve drug stability and avert the aggregation of the magnetic nanoparticles. In this work, two magnetoliposome architectures, solid and aqueous, were combined with supramolecular peptide-based hydrogels, which are of biomedical interest owing to their biocompatibility, easy tunability, and wide array of applications. This proof-of-concept was carried out through combination of magnetoliposomes (loaded with the model drug curcumin and the lipid probe Nile Red) with the hydrogels prior to pH triggered gelation, and fluorescence spectroscopy was used to assess the dynamics of the encapsulated molecules. These systems allow for the encapsulation of a wider array of drugs. Further, the local environment of the encapsulated molecules after gelation is unaffected by the used magnetoliposome architecture. This system design is promising for future developments on drug delivery as it provides a means to independently modify the components and adapt and optimize the design according to the required conditions.FCT -Fundação para a Ciência e a Tecnologia(UIDB/00686/2020