Dendrimers in biomedical applications--reflections on the field.

Because of the high catalytic activities and substrate specificity, natural enzymes have been widely used in industrial, medical, and biological fields, etc. Although promising, they often suffer from intrinsic shortcomings such as high cost, low operational stability, and difficulties of recycling. To overcome these shortcomings, researchers have been devoted to the exploration of artificial enzyme mimics for a long time. Since the discovery of ferromagnetic nanoparticles with intrinsic horseradish peroxidase-like activity in 2007, a large amount of studies on nanozymes have been constantly emerging in the next decade. Nanozymes are one kind of nanomaterials with enzymatic catalytic properties. Compared with natural enzymes, nanozymes have the advantages such as low cost, high stability and durability, which have been widely used in industrial, medical, and biological fields. A thorough understanding of the possible catalytic mechanisms will contribute to the development of novel and high-efficient nanozymes, and the rational regulations of the activities of nanozymes are of great significance. In this review, we systematically introduce the classification, catalytic mechanism, activity regulation as well as recent research progress of nanozymes in the field of biosensing, environmental protection, and disease treatments, etc. in the past years. We also propose the current challenges of nanozymes as well as their future research focus. We anticipate this review may be of significance for the field to understand the properties of nanozymes and the development of novel nanomaterials with enzyme mimicking activities.

Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications

Department of Chemistry, Department of Radiology, Washington University in Saint Louis, Saint Louis, Missouri 63130, Department of Chemistry, Texas A&M University, College Station, Texas 77842, Cancer Center Karolinska, Department of Oncology-Pathology CCK, R8:03 Karolinska Hospital and Institute, SE-171 76 Stockholm, Sweden, and Department of Chemistry and Biochemistry, Department of Materials, and Materials Research Laboratory, University of California, Santa Barbara, California 93106

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Applications of Orthogonal “Click” Chemistries in the Synthesis of Functional Soft Materials

Several recent conceptual advances, which take advantage of the design criteria and practical techniques of molecular-level control in organic chemistry, allow preparation of well-defined polymers and nanostructured materials Two trends are clear: the realization that synthesis of complex macromolecules poses major challenges and opportunities and the expectation that such materials will exhibit distinctive properties and functions Polymer synthesis methods now being developed will yield well-defined synthetic macromolecules that are capable of mimicking many of the features of proteins (for example, three-dimensional folded structure) and other natural materials These macromolecules have far-reaching potential for the study of molecular-level behavior at interfaces, in thin films, and in solution, while also enabling the development of encapsulation, drug-delivery, and nanoscale-patterning technologies

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The Convergence of Synthetic Organic and Polymer Chemistries

Responsive polymers in controlled drug delivery

Advanced drug delivery devices via self-assembly of amphiphilic block copolymers

The conjugation of peptides/proteins and synthetic polymers is a useful strategy to overcome some of the limitations related to the use of the individual components. This review will highlight two aspects: enhanced structural control at the nanometer level and improved performance, in particular with respect to biomedical applications. In the former case, peptide sequences are mainly used to mediate self-assembly of synthetic polymers. In the latter case, conjugation of an appropriate synthetic polymer to a pharmaceutically active peptide/protein can, for example, prevent premature enzymatic degradation and enhance blood circulation times, which is therapeutically advantageous.

Peptide/protein hybrid materials: enhanced control of structure and improved performance through conjugation of biological and synthetic polymers.

The self-assembly mechanism has been studied in poly(γ-benzyl-l-glutamate)−poly(ethylene glycol)−poly(γ-benzyl-l-glutamate) (PBLG−PEG−PBLG) triblock copolymer melts using X-ray scattering, polarizing optical microscopy, differential scanning calorimetry, and FTIR spectroscopy. Intrinsic competing interactions (crystallization, hydrogen bonding, liquid crystallinity, microphase separation) give rise to different levels of organization. Depending on the peptide volume fraction f, two cases can be discussed:  for low peptide volume fractions, microphase separation results in PBLG and PEG phases rich in all secondary structures (α-helices, β-sheets, and chain-folded PEG) notwithstanding the large undercooling necessary to induce PEG crystallization. For f > 0.4, interfacial mixing results in the destruction of the less coherent peptide secondary structures (β-sheet). Interfacial mixing may prove to be a key factor in controlling the appearance of β-sheets in low molecular weight peptides.

Hierarchical Self-Assembly of Poly(γ-benzyl-l-glutamate)−Poly(ethylene glycol)−Poly(γ-benzyl-l-glutamate) Rod−Coil−Rod Triblock Copolymers

This paper describes the synthesis and supramolecular organization of two novel hybrid diblock copolymers based on poly(ethylene glycol) (PEG) and peptide sequences inspired by the coiled coil protein folding motif. The self-organization of the diblock copolymers is driven by the tendency of the peptide segments to form well-defined tertiary structures. In contrast to conventional amphiphilic block copolymers, whose self-organization is driven by unspecific hydrophobic interactions and leads to polydisperse aggregates, it was anticipated that this approach could allow precise control over the aggregation number in aqueous solution. Circular dichroism and analytical ultracentrifugation experiments indicated that the self-organization properties of the peptide segments are retained upon conjugation of PEG, and discrete, well-defined supramolecular aggregates are formed. No evidence was found for unspecific self-organization of the diblock copolymers to large polydisperse structures, as it is the case for conventional amphiphilic block copolymers. In contrast, the self-organization of the PEG-b-peptide diblock copolymers is described as an equilibrium between unimeric block copolymer molecules and dimeric and tetrameric coiled coil aggregates. The relative amounts of these species depend on concentration, temperature, solvent, and the molecular weight of the PEG block.

Reversible self-organization of poly(ethylene glycol)-based hybrid block copolymers mediated by a De Novo four-stranded α-helical coiled coil motif

This study investigates the structure and organization of a series of hybrid diblock copolymers based on polyethylene glycol) (PEG) and peptide sequences inspired by the coiled coil protein folding motif. Circular dichroism spectroscopy and analytical ultracentrinigation experiments indicate that the peptide sequences in these block copolymers act as structure-directing auxiliaries and mediate the formation of discrete nanosized assemblies. This self-assembly process is driven by the very specific folding and organization properties of the peptide sequences and does not involve unspedfic interactions leading to large polydisperse structures. The present study also demonstrates that the self-assembly properties of the hybrid block copolymers can be controlled via selective replacement of one or two amino acid residues in the peptide block. This is an attractive feature in view of possible biomedical applications. Preliminary biological experiments show that the properties of these polymers correlate with their self-assembly behavior.

Guido W. M. Vandermeulen

Papers

Advanced drug delivery devices via self-assembly of amphiphilic block copolymers

Peptide/protein hybrid materials: enhanced control of structure and improved performance through conjugation of biological and synthetic polymers.

Hierarchical Self-Assembly of Poly(γ-benzyl-l-glutamate)−Poly(ethylene glycol)−Poly(γ-benzyl-l-glutamate) Rod−Coil−Rod Triblock Copolymers

Reversible self-organization of poly(ethylene glycol)-based hybrid block copolymers mediated by a De Novo four-stranded α-helical coiled coil motif

PEG-based hybrid block copolymers containing α-helical coiled coil peptide sequences: Control of self-assembly and preliminary biological evaluation