TY - JOUR
T1 - Redox-responsive peptide-based complex coacervates as delivery vehicles with controlled release of proteinous drugs
T2 - Communications Chemistry
AU - Wang, J.
AU - Abbas, M.
AU - Huang, Y.
AU - Li, Y.
N1 - Export Date: 11 January 2024; Cited By: 0; Correspondence Address: J. Wang; Department of Radiology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai, 200233, China; email: [email protected]; Y. Huang; Department of Radiology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai, 200233, China; email: [email protected]; Y. Li; Department of Radiology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai, 200233, China; email: [email protected]
PY - 2023
Y1 - 2023
N2 - Proteinous drugs are highly promising therapeutics to treat various diseases. However, they suffer from limited circulation times and severe off-target side effects. Inspired by active membraneless organelles capable of dynamic recruitment and releasing of specific proteins, here, we present the design of coacervates as therapeutic protocells, made from small metabolites (anionic molecules) and simple arginine-rich peptides (cationic motif) through liquid-liquid phase separation. These complex coacervates demonstrate that their assembly and disassembly can be regulated by redox chemistry, which helps to control the release of the therapeutic protein. A model proteinous drugs, tissue plasminogen activator (tPA), can rapidly compartmentalize inside the complex coacervates, and the coacervates formed from peptides conjugated with arginine-glycine-aspartic acid (RGD) motif (a fibrinogen-derived peptide sequence), show selective binding to the thrombus site and thus enhance on-target efficacy of tPA. Furthermore, the burst release of tPA can be controlled by the redox-induced dissolution of the coacervates. Our proof-of-principle complex coacervate system provides insights into the sequestration and release of proteinous drugs from advanced drug delivery systems and represents a step toward the construction of synthetic therapeutic protocells for biomedical applications. © 2023, The Author(s).
AB - Proteinous drugs are highly promising therapeutics to treat various diseases. However, they suffer from limited circulation times and severe off-target side effects. Inspired by active membraneless organelles capable of dynamic recruitment and releasing of specific proteins, here, we present the design of coacervates as therapeutic protocells, made from small metabolites (anionic molecules) and simple arginine-rich peptides (cationic motif) through liquid-liquid phase separation. These complex coacervates demonstrate that their assembly and disassembly can be regulated by redox chemistry, which helps to control the release of the therapeutic protein. A model proteinous drugs, tissue plasminogen activator (tPA), can rapidly compartmentalize inside the complex coacervates, and the coacervates formed from peptides conjugated with arginine-glycine-aspartic acid (RGD) motif (a fibrinogen-derived peptide sequence), show selective binding to the thrombus site and thus enhance on-target efficacy of tPA. Furthermore, the burst release of tPA can be controlled by the redox-induced dissolution of the coacervates. Our proof-of-principle complex coacervate system provides insights into the sequestration and release of proteinous drugs from advanced drug delivery systems and represents a step toward the construction of synthetic therapeutic protocells for biomedical applications. © 2023, The Author(s).
U2 - 10.1038/s42004-023-01044-8
DO - 10.1038/s42004-023-01044-8
M3 - Article
SN - 2399-3669
VL - 6
JO - Commun. Chem.
JF - Commun. Chem.
IS - 1
ER -