Synthesis of Hybrid-Polypeptides m-PEO-b-poly(His-co-Gly) and m-PEO-b-poly(His-co-Ala) and Study of Their Structure and Aggregation. Influence of Hydrophobic Copolypeptides on the Properties of Poly(L-histidine)

Skoulas, Dimitrios; Stavroulaki, Dimitra; Santorinaios, Konstantinos; Iatrou, Hermis

doi:10.3390/polym9110564

Cited by 10 publications

(7 citation statements)

References 45 publications

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“…Yield Synthesis of glycine NCA (Gly NCA). Glycine NCA was synthesised using a modified procedure from previously reported literature 63 . Glycine (67 mmol, 5 g) was suspended within a mixture of 250 mL of anhydrous THF and 21.2 mL (+)-αpinene (133 mmol)in a two-necked round bottom flask under argon.…”

Section: Discussionmentioning

confidence: 99%

Spider-silk inspired polymeric networks by harnessing the mechanical potential of β-sheets through network guided assembly

Chan

Tan

et al. 2020

Nat Commun

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The high toughness of natural spider-silk is attributed to their unique β-sheet secondary structures. However, the preparation of mechanically strong β-sheet rich materials remains a significant challenge due to challenges involved in processing the polymers/proteins, and managing the assembly of the hydrophobic residues. Inspired by spider-silk, our approach effectively utilizes the superior mechanical toughness and stability afforded by localised βsheet domains within an amorphous network. Using a grafting-from polymerisation approach within an amorphous hydrophilic network allows for spatially controlled growth of poly (valine) and poly(valine-r-glycine) as β-sheet forming polypeptides via N-carboxyanhydride ring opening polymerisation. The resulting continuous β-sheet nanocrystal network exhibits improved compressive strength and stiffness over the initial network lacking β-sheets of up to 30 MPa (300 times greater than the initial network) and 6 MPa (100 times greater than the initial network) respectively. The network demonstrates improved resistance to strong acid, base and protein denaturants over 28 days.

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Section: Discussionmentioning

confidence: 99%

Spider-silk inspired polymeric networks by harnessing the mechanical potential of β-sheets through network guided assembly

Chan

Tan

et al. 2020

Nat Commun

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“…Recently, we have demonstrated the controlled polymerization of histidine. Poly( l -histidine) (PHIS) is the only pH-responsive among all homopolypeptides that undergoes a solubility transition within the physiological and tumor tissue pH and possesses many of the desired properties envisaged for the hydrogel. − …”

Section: Introductionmentioning

confidence: 99%

Self-Healing pH- and Enzyme Stimuli-Responsive Hydrogels for Targeted Delivery of Gemcitabine To Treat Pancreatic Cancer

et al. 2018

Self Cite

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A novel, multifunctional hydrogel that exhibits a unique set of properties for the effective treatment of pancreatic cancer (PC) is presented. The material is composed of a pentablock terpolypeptide of the type PLys- b-(PHIS- co-PBLG)-PLys- b-(PHIS- co-PBLG)- b-PLys, which is a noncytotoxic polypeptide. It can be implanted via the least invasive route and selectively delivers gemcitabine to efficiently treat PC. Simply mixing the novel terpolypeptide with an aqueous solution of gemcitabine within a syringe results in the facile formation of a hydrogel that has the ability to become liquid under the shear rate of the plunger. Upon injection in the vicinity of cancer tissue, it immediately reforms into a hydrogel due to the unique combination of its macromolecular architecture and secondary structure. Because of its pH responsiveness, the hydrogel only melts close to PC; thus, the drug can be delivered directionally toward the cancerous rather than healthy tissues in a targeted, controlled, and sustained manner. The efficacy of the hydrogel was tested in vivo on human to mouse xenografts using the drug gemcitabine. It was found that the efficacy of the hydrogel loaded with only 40% of the drug delivered in one dose was equal to or slightly better than the peritumoral injection of 100% of the free drug delivered in two doses, the typical chemotherapy used in clinics so far. This result suggests that the hydrogel can direct the delivery of the encapsulated drug effectively in the tumor tissue. Enzymes lead to its biodegradation, avoiding removal by resection of the polypeptidic carrier after cargo delivery. The unique properties of the hydrogel formed can be predetermined through its molecular characteristics, rendering it a promising modular material for many biological applications.

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“…PC4 is composed of 13 alternating hydrophilic (His and Gly) and hydrophobic (Val, Leu, and Tyr) residues that may drive the formation of β-sheet structures with a hydrophobic face on one side and a hydrophilic face on the other in aqueous media ( Figure 1 A). A previous report using poly(Gly) incorporated with poly(His) confirmed the formation of a β-sheet hydrogel via hydrophobic aggregation [ 37 ]. It is very likely that the high content of Gly presented in the PC4 peptide may also be the driving force of β-sheet formation due to the increased hydrophobicity.…”

Section: Resultsmentioning

confidence: 88%

Bioinspired Sandcastle Worm-Derived Peptide-Based Hybrid Hydrogel for Promoting the Formation of Liver Spheroids

Chen

Wang

et al. 2022

Gels

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The generation of hepatic spheroids is beneficial for a variety of potential applications, including drug development, disease modeling, transplantation, and regenerative medicine. Natural hydrogels are obtained from tissues and have been widely used to promote the growth, differentiation, and retention of specific functionalities of hepatocytes. However, relying on natural hydrogels for the generation of hepatic spheroids, which have batch to batch variations, may in turn limit the previously mentioned potential applications. For this reason, we researched a way to establish a three-dimensional (3D) culture system that more closely mimics the interaction between hepatocytes and their surrounding microenvironments, thereby potentially offering a more promising and suitable system for drug development, disease modeling, transplantation, and regenerative medicine. Here, we developed self-assembling and bioactive hybrid hydrogels to support the generation and growth of hepatic spheroids. Our hybrid hydrogels (PC4/Cultrex) inspired by the sandcastle worm, an Arg-Gly-Asp (RGD) cell adhesion sequence, and bioactive molecules derived from Cultrex BME (Basement Membrane Extract). By performing optimizations to the design, the PC4/Cultrex hybrid hydrogels can enhance HepG2 cells to form spheroids and express their molecular signatures (e.g., Cyp3A4, Cyp7a1, A1at, Afp, Ck7, Ck1, and E-cad). Our study demonstrated that this hybrid hydrogel system offers potential advantages for hepatocytes in proliferating, differentiating, and self-organizing to form hepatic spheroids in a more controllable and reproducible manner. In addition, it is a versatile and cost-effective method for 3D tissue cultures in mass quantities. Importantly, we demonstrate that it is feasible to adapt a bioinspired approach to design biomaterials for 3D culture systems, which accelerates the design of novel peptide structures and broadens our research choices on peptide-based hydrogels.

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Synthesis of Hybrid-Polypeptides m-PEO-b-poly(His-co-Gly) and m-PEO-b-poly(His-co-Ala) and Study of Their Structure and Aggregation. Influence of Hydrophobic Copolypeptides on the Properties of Poly(L-histidine)

Cited by 10 publications

References 45 publications

Spider-silk inspired polymeric networks by harnessing the mechanical potential of β-sheets through network guided assembly

Spider-silk inspired polymeric networks by harnessing the mechanical potential of β-sheets through network guided assembly

Self-Healing pH- and Enzyme Stimuli-Responsive Hydrogels for Targeted Delivery of Gemcitabine To Treat Pancreatic Cancer

Bioinspired Sandcastle Worm-Derived Peptide-Based Hybrid Hydrogel for Promoting the Formation of Liver Spheroids

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