Home > Articles > Published articles > Probing the Biosafety of Implantable Artificial Secretory Granules for the Sustained Release of Bioactive Proteins |
Date: | 2023 |
Abstract: | Among bio-inspired protein materials, secretory protein microparticles are of clinical interest as self-contained, slow protein delivery platforms that mimic secretory granules of the human endocrine system, in which the protein is both the drug and the scaffold. Upon subcutaneous injection, their progressive disintegration results in the sustained release of the building block polypeptides, which reach the bloodstream for systemic distribution and subsequent biological effects. Such entities are easily fabricated in vitro by Zn-assisted cross-molecular coordination of histidine residues. Using cationic Zn for the assembly of selected pure protein species and in the absence of any heterologous holding material, these granules are expected to be nontoxic and therefore adequate for different clinical uses. However, such presumed biosafety has not been so far confirmed and the potential protein dosage threshold not probed yet. By selecting the receptor binding domain (RBD) from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein as a model protein and using a mouse lab model, we have explored the toxicity of RBD-made secretory granules at increasing doses up to ∼100 mg/kg of animal weight. By monitoring body weight and biochemical blood markers and through the histological scrutiny of main tissues and organs, we have not observed systemic toxicity. Otherwise, the bioavailability of the material was demonstrated by the induction of specific antibody responses. The presented data confirm the intrinsic biosafety of artificial secretory granules made by recombinant proteins and prompt their further clinical development as self-contained and dynamic protein reservoirs. |
Grants: | Agència de Gestió d'Ajuts Universitaris i de Recerca 2020/PANDE-00003 Agencia Estatal de Investigación PID2019-105416RB-I00 Agencia Estatal de Investigación PDC2022-133858-I00 Agencia Estatal de Investigación PID2020-116174RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00092 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01140 Instituto de Salud Carlos III P21/00150 Ministerio de Sanidad y Consumo CB06/01/0014 Ministerio de Sanidad y Consumo CB06/01/1031 |
Note: | Altres ajuts: acords transformatius de la UAB |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Subject: | Drug delivery ; Protein engineering ; Protein materials ; Recombinant protein ; Self-assembling |
Published in: | ACS applied materials & interfaces, Vol. 15, Issue 33 (August 2023) , p. 39167-39175, ISSN 1944-8252 |
9 p, 6.6 MB |