Protein-responsive protein release of supramolecular/polymer hydrogel composite integrating enzyme activation systems

Abstract

Non-enzymatic proteins including antibodies function as biomarkers and are used as biopharmaceuticals in several diseases. Protein-responsive soft materials capable of the controlled release of drugs and proteins have potential for use in next-generation diagnosis and therapies. Here, we describe a supramolecular/agarose hydrogel composite that can release a protein in response to a non-enzymatic protein. A non-enzymatic protein-responsive system is developed by hybridization of an enzyme-sensitive supramolecular hydrogel with a protein-triggered enzyme activation set. In situ imaging shows that the supramolecular/ agarose hydrogel composite consists of orthogonal domains of supramolecular fibers and agarose, which play distinct roles in protein entrapment and mechanical stiffness, respectively. Integrating the enzyme activation set with the composite allows for controlled release of the embedded RNase in response to an antibody. Such composite hydrogels would be promising as a matrix embedded in a body, which can autonomously release biopharmaceuticals by sensing biomarker proteins.

Biomedical Applications of Supramolecular Materials in the Controllable Delivery of Steroids

“…Secondly, efforts are needed to develop bio-signaling-based release mechanisms. In tumors and some inflammatory diseases (Zhang et al, 2020b), the pH (Deirram et al, 2019), temperature (Zavgorodnya et al, 2017), redox potential (Raza et al, 2018), and even specific overexpressed proteins (Shigemitsu et al, 2020) could serve as stimulations to trigger the drug release of supramolecular materials. Besides, other steroid drugs and macromolecular drugs have been poorly developed in supramolecular materials (Geng et al, 2020).…”

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

“…Similar hydrogel design could be applied for the delivery of GFs to promote bone regeneration as increased levels in MMP-2 protein expression have been detected in the fracture callus during bone fracture repair [ 84 ]. Two diphenylalanine derived peptides with acetoxybenzyl-oxycarbonyl (APmoc-F(CF 3 )F-OH) or benzoate (Bz-FF-OH) groups tethered at the N-terminus were synthesized to obtain enzyme-sensitive supramolecular hydrogels [ 79 ]. Cleavage of N-terminal moiety decreased the hydrophobicity leading to the gel-sol transition.…”

Thiophosphopeptides Instantly Targeting Golgi Apparatus and Selectively Killing Cancer Cells

“…These thiophosphopeptides also may serve as the substrates for thiol-click chemistry 47 or for integration thiol groups in other supramolecular assemblies. [48][49][50][51][52]…”