Dataset Information

Robust drug bioavailability and safety for rheumatoid arthritis therapy using D-amino acids-based supramolecular hydrogels.

ABSTRACT: Long-term use of disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX) shows clinical benefits for rheumatoid arthritis (RA) treatment. However, there are growing concerns over the adverse effects of systemic drug administration. Therefore, a strategy that can enhance drug bioavailability while minimizing side effects is urgently needed, but remains a challenge in RA therapy. To this end, here we conjugated MTX with a supramolecular self-assembling hydrogel composed of d-amino acids with a sequence of G^DF^DF^DY. It was shown that MTX-G^DF^DF^DY hydrogels exhibited a favorable drug selectivity behavior that they increased MTX toxicity toward RA synoviocytes, but reduce toxicity toward normal cells. Moreover, MTX-G^DF^DF^DY hydrogels not only effectively inhibited the proliferation and migration of RA synoviocytes, but also inhibited the polarization of proinflammatory M1 type macrophages to reduce inflammation. After intra-articularly injected the hydrogels into the joints of adjuvant induced arthritis (AIA) mice, we found that MTX-G^DF^DF^DY hydrogels significantly alleviated RA syndromes of joint swelling and fever compared to L-configuration MTX-GFFY hydrogels and free MTX. Furthermore, MTX-G^DF^DF^DY hydrogels successfully protected cartilage though inhibiting synovial invasion and inflammation without causing systematic side effects. Therefore, d-amino acids supramolecular hydrogels can serve as an efficient and safe drug delivery system, showing a promising potential to improve RA therapy.

SUBMITTER: Ma S

PROVIDER: S-EPMC9157599 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Robust drug bioavailability and safety for rheumatoid arthritis therapy using D-amino acids-based supramolecular hydrogels.

Ma Shaodan S Gu Shunan S Zhang Jinwei J Qi Weizhong W Lin Zhaowei Z Zhai Weicheng W Zhan Jie J Li Qi Q Cai Yanbin Y Lu Yao Y

Materials today. Bio 20220519

Long-term use of disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX) shows clinical benefits for rheumatoid arthritis (RA) treatment. However, there are growing concerns over the adverse effects of systemic drug administration. Therefore, a strategy that can enhance drug bioavailability while minimizing side effects is urgently needed, but remains a challenge in RA therapy. To this end, here we conjugated MTX with a supramolecular self-assembling hydrogel composed of d-ami ...[more]

PMID: 35665233

Similar Datasets

Project description:The unique physiochemical properties and multiscale organization of layered materials draw the attention of researchers across a wide range of scientific disciplines. Layered structures are commonly found in diverse biological systems where they fulfill various functions. A prominent example of layered biological materials is the organization of proteins and polypeptides into the archetypal aggregated amyloidal structures. While the organization of proteins into amyloid structures was initially associated with various degenerative disorders, it was later revealed that proteins not related to any disease could also form identical layered assemblies. Thus, it appears that the ability of peptides and proteins to produce amyloid-like aggregates represents a generic property of polyamides to assemble into higher order fibrillar structures. In the aggregated state, the peptide backbone forms β-sheet structures which are further organized into layered arrangements. We have recently extended the identified amyloidogenic building blocks to include not only peptides or proteins, but also single amino acids and other metabolites. High resolution spectroscopy and crystallography analyses confirm the clear potential of amino acids and other metabolites to form layered amyloid-like aggregates showing biophysical and biochemical properties similar to protein amyloids. Therefore, the generic propensity of peptides and proteins backbones to assemble into layered organizations may emanate from their basic building block, the amino acid. In this Account, we aim to introduce the concept of supramolecular β-sheet organization of single amino acids and to present an analysis of their layered-structure organization based on single crystal structures. We demonstrate that, despite the different side-chains that considerably vary in their chemical properties, all coded amino acids display a layer-like assembly stabilized by α-amine to α-carboxyl H-bonds, resembling supramolecular β-sheet structures, while the side-chains determine the higher order organization of the layers. Our work presents the first analysis of the β-sheet propensity of single amino acids in their unbound form, indicating an evolutionary predisposition. We classify the amino acids β-sheet propensity on the basis of the interlayer separation distance in the crystal packing, which correlates well with previously reported classifications based on various criteria, such as hydrophobicity, steric bulkiness, and folding. In addition, we demonstrate that the relative direction of α-amine to α-carboxyl H-bonding pattern provides critical insights regarding the stabilization of parallel versus antiparallel β-sheet structures by the various amino acids. Taken together, our analysis of amino acid crystals provides substantial information regarding protein folding and dynamics and could serve as basic rules set for the design of potential building blocks for molecular self-assembly to produce functional materials of tunable properties, an important objective of bottom-up nanotechnology.

Dataset Information

Robust drug bioavailability and safety for rheumatoid arthritis therapy using D-amino acids-based supramolecular hydrogels.

Publications

Robust drug bioavailability and safety for rheumatoid arthritis therapy using D-amino acids-based supramolecular hydrogels.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets