Macromolecular Bioscience

Cover: Cell surface display of enzymes as whole-cell catalysts may be a better choice in comparison with typical enzyme catalysts because of advantages like autonomous replication, preventing the toxicity of the expressed proteins, the stabilization of the displayed enzymes due to self-immobilization on the cells, and so on. The present manuscript focuses on functionally active expression of poly[(R)-3-hydroxybutyrate] (PHB) depolymerase on the cell surface of E. coli and its potential use as a biocatalyst for (R)-3-hydroxybutyrate (3HB) monomer production from insoluble PHB. Further details can be found in the article by T. Hiraishi,* K. Yamashita, M. Sakono, J. Nakanishi, L.-T. Tan, K. Sudesh, H. Abe, and M. Maeda* on page 218.

The goal of copolymer-based drug delivery systems is to deploy therapeutics intact to specifically targeted tissue of the body through a medium capable of controlling the therapy's administration by means of either a physiological or chemical trigger. To this end, scientists are examining copolymer micelles, polymersomes and hydrogels.

The free-radical miniempulsion copolymerization of BMDO with styrene and MMA is investigated; the obtained polyester and polyester/polystyrene nanoparticles show good uptake into cells and no toxicity. Nanoparticles with incorporated paclitaxel as a hydrophobic drug reveal their potential as a degradable drug delivery system.

Heparin associated with nanoparticles composed of chitosan and cyclodextrins is investigated for a new application as an antiasthmatic drug. The capacity of the nanoparticles to interact with mastocytes and to prevent the degranulation of mast cells confirms the potential interest of this new nanomedicine for the treatment of asthma.

Docetaxel loading into nanoparticles of propyl starch, a novel hydrophobic starch derivative, is described. The nanoparticles exhibit a high docetaxel encapsulation and the ability to control its release. Cellular cytotoxicity assays indicate safety and efficacy of nanoparticles over non-encapsulated drug at the test concentrations. Uptake investigations indicate an efficient uptake and peri-nuclear localization of nanoparticles by cancer cells.

High aspect ratio fibrillar nanoscale arrays are generated from an α-helical fiber. The design is inspired by an intermittence effect observed for native β-structured α-synunclein fibrils. The generated nanoarrays extend to microns in length and are composed of periodic nanosized segments separated at uniform distances of unfolded regions.

Hybrid hyaluronic acid–gelatin (HA–Ge) hydrogel particles are embedded in a secondary HA network. The microgels are sufficiently stiff, with the amino acid sequences required for cell adhesion. The soft external network of hyaluronic acid can facilitate non-proteolytic cell migration. The microgel system exhibits pH responsiveness. The HA–Ge hierarchical system characteristics are favorable for tissue engineering applications.

Novel PHEMA derivatives for mammalian cell culture are synthesized and characterized. Among the polymers, a PHEMA derivative with highest oxygen content (PHEMAAA) shows its ability to promote human dermal fibroblast cell adhesion and proliferation while effectively decreasing bacterial adhesion.

The display of PHB depolymerase (PhaZ_RpiT1) on the surface of E. coli is realized using OprI from P. aeruginosa. The displayed PhaZ_RpiT1 retained its cleaving ability for soluble substrates as well as its adsorbing ability to PHB surface. The displayed enzyme also retains its inherent ability to degrade PHB, demonstrating its potential use for (R)-3-hydroxybutyrate production from PHB materials.

Results obtained from molecular dynamics simulations of high-generation PAMAM-based dendrimers having NH₃and triethanolamine as cores, forming complexes with a short interfering RNA at different pH values and at physiological ionic strength, are reported. The structural flexibility of the triethanolamine-core dendrimer allows a higher degree of penetration of the siRNA strands within the dendritic structure resulting in the formation of more stable complexes.

Biodegradable electroactive hydrogel (AP-g-GA), aniline pentamer (AP) grafting gelatin (GA), is synthesized. The hydrophobic AP changes the hydrogel's porous structure of the natural GA. With increasing content of AP, the hydrogel gradually forms porous structures, from “honeycomb” to “bamboo raft”. The AP-g-GA polymers can accelerate the proliferation of osteoblasts compared with pure GA and TCPS.

A multifunctional drug carrier based on polypseudorotaxane(PEG/CD)-nanogated mesoporous silica is presented. It combines multifunctionality, i.e., enhanced tumor-specific cellular uptake, intracellular delivery, biocompatibility, and potential in vivo longevity in one nanoparticle and offers therefore a huge potential in targeting tumor therapy.

The pre-polymer poly(but-2-ene-1,4-diyl malonate) (PBM) and an array of PBM-based materials are shown to be degradable under physiological conditions in vitro with control over the formed degradation products. The PBM-based materials thus have potential as materials for future biomedical applications.

Genetically engineered, β-sheet-containing fibrils can be platinated via reductive metallization. Localization of the platinum nanoparticles along the fibril edges is determined by transmission electron microscopy and energy dispersive X-ray data analysis. The platinated fibrils exhibit clear evidence of metallization at the functionalized turn-residues of the fibrillar constructs.