Dual-Responsive Glycopolymers for Intracellular Codelivery of Antigen and Lipophilic Adjuvants

Autor: Judith De Mel, Mehjabeen Hossain, Oluwaseyi Shofolawe-Bakare, Sk Arif Mohammad, Emily Rasmussen, Khadeeja Milloy, Micaela Shields, Eric W. Roth, Karan Arora, Rafael Cueto, Shou-Ching Tang, John T. Wilson, Adam E. Smith, Thomas A. Werfel
Rok vydání: 2022
Předmět:
Zdroj: Molecular Pharmaceutics. 19:4705-4716
ISSN: 1543-8392
1543-8384
Popis: Traditional approaches to vaccines use whole organisms to trigger an immune response, but they do not typically generate robust cellular-mediated immunity and have various safety risks. Subunit vaccines composed of proteins and/or peptides represent an attractive and safe alternative to whole organism vaccines, but they are poorly immunogenic. Though there are biological reasons for the poor immunogenicity of proteins and peptides, one other key to their relative lack of immunogenicity could be attributed to the poor pharmacokinetic properties of exogenously delivered proteins and peptides. For instance, peptides often aggregate at the site of injection and are not stable in biological fluids, proteins and peptides are rapidly cleared from circulation, and both have poor cellular internalization and endosomal escape. Herein, we developed a delivery system to address the lack of protein immunogenicity by overcoming delivery barriers as well as codelivering immune-stimulating adjuvants. The glycopolymeric nanoparticles (glycoNPs) are composed of a dual-stimuli-responsive block glycopolymer, poly[2-(diisopropylamino)ethyl methacrylate]
Databáze: OpenAIRE