Institute of Materials Science and Nanotechnology (UNAM)

Permanent URI for this communityhttps://hdl.handle.net/11693/115649

Browse

Now showing 1 - 4 of 4

Open Access
Amphiphilic RGD and GHK peptides synergistically enhance liposomal delivery into cancer and endothelial cells
(Royal Society of Chemistry, 2021-09-28) Zoughaib, M.; Pavlov, R. V.; Gaynanova, G. A.; Garifullin, Ruslan; Evtugynd, V. G.; Abdullin, T. I.
This study reveals enhanced cancer-targeting properties of a peptide composition consisting of RGD and GHK, recognized as an important cell adhesion factor and pleiotropic modulator of cellular functions, respectively. C12-GGRGD-NH2 and C12-GGGHK-NH2 amphiphilic peptides comprising a lauric acid moiety capable of insertion into the liposomal membrane were synthesized. Composite liposomes made of phosphatidylcholine, cationic DOTAP and the peptide(s) were used at a pre-optimized PC : DOTAP ratio of 35 : 1 and relative peptide content of 4 mol%. The RGD/GHK dual targeting system exhibited a profound synergistic effect on the cellular uptake of the liposomal formulation in integrin-overexpressing cancer and endothelial cells. Effective liposome activation via in situ association of the amphiphilc peptide(s) with the liposomal membrane was carried out. Dual peptide-modified liposomes loaded with doxorubicin or paclitaxel induced enhanced cytotoxicity accompanied by oxidative stress and mitochondria depolarization in the target cells. The study shows joint potential of RGD and GHK tripeptides as a targeting system in anticancer/antiangiogenic therapy and provides a methodology for screening of combinatorial effects of bioactive peptides displayed on the liposome surface. Peptide-modified liposomes were employed to reveal GHK–heparin binding, suggesting a potential complementary role of glycosaminoglycans in RGD/GHK-mediated liposomal delivery.
Open Access
Enhanced angiogenic effects of RGD, GHK peptides and copper (II) compositions in synthetic cryogel ECM model
(Elsevier, 2020) Zoughaib, M.; Luong, D.; Garifullin, Ruslan; Gatina, D. Z.; Fedosimova, S. V.; Abdullin, T. I.
Synthetic oligopeptides are a promising alternative to natural full-length growth factors and extracellular matrix (ECM) proteins in tissue regeneration and therapeutic angiogenesis applications. In this work, angiogenic properties of dual and triple compositions containing RGD, GHK peptides and copper (II) ions (Cu2+) were for the first time studied. To reveal specific in vitro effects of these compositions in three-dimensional scaffold, adamantyl group bearing peptides, namely Ada-Ahx-GGRGD (1) and Ada-Ahx-GGGHK (2), were effectively immobilized in bioinert pHEMA macroporous cryogel via host-guest β-cyclodextrin-adamantane interaction. The cryogels were additionally functionalized with Cu2+ via the formation of GHK-Cu complex. Angiogenic responses of HUVECs grown within the cryogel ECM model were analyzed. The results demonstrate that the combination of RGD with GHK and further with Cu2+ dramatically increases cell proliferation, differentiation, and production of a series of angiogenesis related cytokines and growth factors. Furthermore, the level of glutathione, a key cellular antioxidant and redox regulator, was altered in relation to the angiogenic effects. These results are of particular interest for establishing the role of multiple peptide signals on regeneration related processes and for developing improved tissue engineering materials.
Open Access
In situ functionalization of poly(hydroxyethyl methacrylate) cryogels with oligopeptides via β-Cyclodextrin–adamantane complexation for studying cell-instructive peptide environment
(American Chemical Society, 2020) Luong, T. D.; Zoughaib, M.; Garifullin, Ruslan; Kuznetsova, S.; Güler, Mustafa O.; Abdullin, T. I.
Oligopeptides are versatile cell modulators resembling pleiotropic activities of ECM proteins and growth factors. Studying the role of cellinstructive peptide signals within 3D scaffolds, yet poorly known, requires effective approaches to introducing bioactive sequences into appropriate materials. We synthesized RGD and GHK motif based peptides 1 and 2 linked to the terminal adamantyl group (Ad) and their fluorescent derivatives 3 and 4. Poly(hydroxyethyl methacrylate) (pHEMA) cryogels with additional PEG/β- cyclodextrin (CD) units were prepared as an inert macroporous scaffold capable to bind the adamantylated peptides via affinity CD-Ad complexation. According to toluidine blue staining, the CD moieties were effectively and stably incorporated in the pHEMA cryogels at nanomolar amounts per milligram of material. The CD component gradually increased the thickness and swelling ability of the polymer walls of cryogels, resulting in a noticeable decrease in macropore size and modulation of viscoelastic properties. The labeled peptides exhibited fast kinetics of specific binding to the CD-modified cryogels and were simultaneously immobilized by coincubation. The peptide loading approached ca. 0.31 mg per cm2 of cryogel sheet. A well-defined mitogenic effect of the immobilized peptides (2 < 1≪ 1 + 2) was revealed toward 3T3 and PC-12 cells. The synergistic action of RGD and GHK peptides induced a profound change in cell behavior/morphology attributed to a growth-factor-like activity of the composition. Altogether, our results provide an effective procedure for the preparation of CDmodified pHEMA cryogels and their uniform in situ functionalization with bioactive peptide(s) of interest and an informative study of cellular responses in the functionalized scaffolds
Open Access
Triphenylphosphonium moiety modulates proteolytic stability and potentiates neuroprotective activity of antioxidant tetrapeptides in vitro
(Frontiers Media S.A., 2018) Akhmadishina, R. A.; Garifullin, R.; Petrova, N. V.; Kamalov, M. I.; Abdullin, T. I.
Although delocalized lipophilic cations have been identified as effective cellular and mitochondrial carriers for a range of natural and synthetic drug molecules, little is known about their effects on pharmacological properties of peptides. The effect of triphenylphosphonium (TPP) cation on bioactivity of antioxidant tetrapeptides based on the model opioid YRFK motif was studied. Two tetrapeptide variants with L-arginine (YRFK) and D-arginine (YrFK) were synthesized and coupled with carboxyethyl-TPP (TPP-3) and carboxypentyl-TPP (TPP-6) units. The TPP moiety noticeably promoted YRFK cleavage by trypsin, but effectively prevented digestion of more resistant YrFK attributed, respectively, to structure-organizing and shielding effects of the TPP cation on conformational variants of the tetrapeptide motif. The TPP moiety enhanced radical scavenging activity of the modified YRFK in a model Fenton-like reaction, whereas decreased reactivity was revealed for both YrFK and its TPP derivative. The starting motifs and modified oligopeptides, especially the TPP-6 derivatives, suppressed acute oxidative stress in neuronal PC-12 cells during a brief exposure similarly with glutathione. The effect of oligopeptides was compared upon culturing of PC-12 cells with CoCl2, L-glutamic acid, or menadione to mimic physiologically relevant oxidative states. The cytoprotective activity of oligopeptides significantly depended on the type of oxidative factor, order of treatment and peptide structure. Pronounced cell-protective effect was established for the TPP-modified oligopeptides, which surpassed that of the unmodified motifs. The protease-resistant TPP-modified YrFK showed the highest activity when administered 24 h prior to the cell damage. Our results suggest that the TPP cation can be used as a modifier for small therapeutic peptides to improve their pharmacokinetic and pharmacological properties.

Browse

Browsing Institute of Materials Science and Nanotechnology (UNAM) by Author "Abdullin, T. I."