Supramolecular biomaterials

Webber, Matthew J.; Appel, Eric A.; Meijer, E. W.; Langer, Robert

doi:10.1038/nmat4474

Cited by 1,279 publications

(957 citation statements)

References 170 publications

Supporting

Mentioning

952

Contrasting

Unclassified

Order By: Relevance

“…Based on a generic set of genetic engineering procedures, recombinant protein production has largely impacted on biotechnological and biopharmaceutical industries, with more than 400 protein drugs approved for human use [1]. The identification [2,3] and exploitation [4,5] of oligomerization domains, the tailored fibrillation of amyloidal protein forms [6] and the de novo design of protein-protein interacting patches [7,8] offer a wide spectrum of possibilities regarding the generation of supramolecular materials to be used in biological interfaces [9][10][11]. Being functional but also biocompatible and biodegradable, protein materials show a still unexplored biomedical potential in both regenerative medicine and conventional or cell-targeted drug delivery [12,13].…”

Section: Introductionmentioning

confidence: 99%

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

et al. 2017

View full text Add to dashboard Cite

Self-assembling proteins are gaining attention as building blocks for application-tailored nanoscale materials. This is mostly due to the biocompatibility, biodegradability, and functional versatility of peptide chains. Such a potential for adaptability is particularly high in the case of recombinant proteins, which are produced in living cells and are suitable for genetic engineering. However, how the cell factory itself and the particular protein folding machinery influence the architecture and function of the final material is still poorly explored. In this study we have used diverse analytical approaches, including small-angle X-ray scattering (SAXS) and field emission scanning electron microscopy (FESEM) to determine the fine architecture and geometry of recombinant, tumor-targeted protein nanoparticles of interest as drug carriers, constructed on a GFP-based modular scheme. A set of related oligomers were produced in alternative Escherichia coli strains with variant protein folding networks. This resulted in highly regular populations of morphometric types, ranging from 2.4 to 28 nm and from spherical- to rod-shaped materials. These differential geometric species, whose relative proportions were determined by the features of the producing strain, were found associated with particular fluorescence emission, cell penetrability and receptor specificity profiles. Then, nanoparticles with optimal properties could be analytically identified and further isolated from producing cells for use. The cell’s protein folding machinery greatly modulates the final geometry reached by the constructs, which in turn defines the key parameters and biological performance of the material.Peer ReviewedPostprint (author's final draft

show abstract

Section: Introductionmentioning

confidence: 99%

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Direct covalent modification, although demonstrating efficacy in altering the stability and function of protein drugs, introduces complications from the need to isolate and purify the modified protein following labeling as well as the possibility that introduction of an exogenous moiety could lead to immunogenicity or a deleterious effect on protein function and signaling. Supramolecular chemistry has broad potential application for biology and medicine by leveraging specific, directional, and reversible noncovalent molecular recognition motifs (14). Hostguest motifs, for example, typically comprise a discrete macrocyclic host with a cavity that is selective for complementary binding to certain guest ligands (15).…”

mentioning

confidence: 99%

Supramolecular PEGylation of biopharmaceuticals

Webber

Appel

Vinciguerra

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

180

260

View full text Add to dashboard Cite

The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit [7]uril (CB [7])-PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB [7] and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy. supramolecular chemistry | protein engineering | drug delivery | protein formulation

show abstract

“…Such approaches to generate fibers are limited by high energy input, laborious procedures, and intensive use of organic solvents. Supramolecular pathways enable the formation of filamentous soft materials that are showing promise in biomedical applications (4)(5)(6), such as cell culture (7)(8)(9) and tissue engineering (10). However, such materials are constrained by the length scale (submicrometer level) (11)(12)(13), energy intake during production (9), and complex design of assembly units (14).…”

mentioning

confidence: 99%

Bioinspired supramolecular fibers drawn from a multiphase self-assembled hydrogel

Shah

Liu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

120

102

View full text Add to dashboard Cite

Inspired by biological systems, we report a supramolecular polymer-colloidal hydrogel (SPCH) composed of 98 wt % water that can be readily drawn into uniform (∼6-µm thick) "supramolecular fibers" at room temperature. Functionalized polymer-grafted silica nanoparticles, a semicrystalline hydroxyethyl cellulose derivative, and cucurbit[8]uril undergo aqueous self-assembly at multiple length scales to form the SPCH facilitated by host-guest interactions at the molecular level and nanofibril formation at colloidal-length scale. The fibers exhibit a unique combination of stiffness and high damping capacity (60-70%), the latter exceeding that of even biological silks and cellulose-based viscose rayon. The remarkable damping performance of the hierarchically structured fibers is proposed to arise from the complex combination and interactions of "hard" and "soft" phases within the SPCH and its constituents. SPCH represents a class of hybrid supramolecular composites, opening a window into fiber technology through low-energy manufacturing. supramolecular fiber | hydrogel | self-assembly | damping | spider silk I n nature, spiders spin silk fibers with superb properties at ambient temperatures and pressures (1, 2). We have yet to mimic such an elegant process. Conventionally, synthetic fibers are manufactured through a variety of spinning techniques, including wet, dry, gel, and electrospinning (3). Such approaches to generate fibers are limited by high energy input, laborious procedures, and intensive use of organic solvents. Supramolecular pathways enable the formation of filamentous soft materials that are showing promise in biomedical applications (4-6), such as cell culture (7-9) and tissue engineering (10). However, such materials are constrained by the length scale (submicrometer level) (11-13), energy intake during production (9), and complex design of assembly units (14).Here, we report drawing supramolecular fibers of arbitrary length from a dynamic supramolecular polymer-colloidal hydrogel (SPCH) at room temperature (Movie S1). The components consist of methyl viologen (MV)-functionalized polymer-grafted silica nanoparticles (P1), a semicrystalline polymer in the form of a hydroxyethyl cellulose derivative (H1), and cucurbit[8]uril (CB[8]) as illustrated in Fig. 1. The macrocycle CB[8] is capable of simultaneously encapsulating two guests within its cavity, forming a stable yet dynamic ternary complex, and has been exploited as a supramolecular "handcuff" to physical cross-link functional polymers (15-18). Introducing shape-persistent nanoparticles into the supramolecular hydrogel system allows for modification of the local gel structures at the colloidal-length scale, resulting in assemblies with unique emergent properties (19). The hierarchical nature of the SPCH is presented, where the hydrogel is composed of nanoscale fibrillar structures. The self-assembled SPCH composite exhibits great elasticity at a remarkably high water content (98%), showing a low-energy manufacturing process for fibers from natural, ...

show abstract

Supramolecular biomaterials

Cited by 1,279 publications

References 170 publications

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

Supramolecular PEGylation of biopharmaceuticals

Bioinspired supramolecular fibers drawn from a multiphase self-assembled hydrogel

Contact Info

Product

Resources

About