Journal article
Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes
University of Massachusetts1
Department of Health Technology, Technical University of Denmark2
Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark3
Colloids & Biological Interfaces, Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark4
Delivering peptides and proteins with intracellular function represents a promising avenue for therapeutics, but remains a challenge due to the selective permeability of the plasma membrane. The successful delivery of cytosolically active proteins would enable many opportunities, including improved vaccine development through major histocompatibility complex (MHC) class I antigen display.
Extended research using cell-penetrating peptides (CPPs) has aimed to facilitate intracellular delivery of exogenous proteins with some success. A new class of polymer-based mimics termed protein transduction domain mimics (PTDMs), which maintain the positive charge and amphiphilic nature displayed by many CPPs, was developed using a poly-norbornene-based backbone.
Herein, we use a previously characterized PTDM to investigate delivery of the model antigen SIINFEKL into leukocytes. Peptide delivery into over 90% of CD14+ monocytes was detected in less than 15 min with nominal inflammatory cytokine response and high cell viability. The co-delivery of a TLR9 agonist and antigen using the PTDM into antigen presenting cells in vitro showed presentation of SIINFEKL in association with MHC class I molecules, in addition to upregulation of classical differentiation markers revealing the ability of the PTDM to successfully deliver cargo intracellularly and show application in the field of immunotherapy.
Language: | English |
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Publisher: | American Chemical Society |
Year: | 2019 |
Pages: | 2462-2469 |
ISSN: | 15438392 and 15438384 |
Types: | Journal article |
DOI: | 10.1021/acs.molpharmaceut.9b00070 |
ORCIDs: | 0000-0003-3277-7925 and Andresen, Thomas L. |
Antigen Presentation Cell Survival Cell-Penetrating Peptides Dendritic Cells Flow Cytometry Healthy Volunteers Histocompatibility Antigens Class I Humans Lipopolysaccharide Receptors MHC class I presentation Monocytes THP-1 Cells TLR9 protein, human Toll-Like Receptor 9 antigen delivery cell penetrating peptide mimics monocytes