Immunopolymer Lipid Nanoparticles for Delivery of Macromolecules to Antigen-Expressing Cells.
Abstract
Macromolecules such as antibodies and antibody fragments have been reported to interfere with intracellular targets, but their use is limited to delivery systems where expression is achieved from vectors such as plasmids or viruses. We have developed PEGylated nanoparticles of poly-lactic acid (PLA), including the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which are functionalized with monoclonal anti-CD7, anti-CD53, or anti-GPR56 antibodies for receptor-mediated endocytic delivery into T-cell leukemia cell lines. Incorporation of DOTAP as the lipid component of the PLA nanoparticles enhanced the release of the immuno-nanoparticles from the endosomes into the cytosol compared to nanoparticles made from PLA alone. Systemic delivery of these anti-CD7 immuno-nanoparticles into humanized CD7 transgenic mice resulted in localization in the spleen, enhanced uptake into CD7-expressing splenocytes, and release of low amounts of reporter mRNA for translation. These functionalized polymer lipid nanoparticles are the basis for elaboration and optimization for realizing their potential in therapeutic applications to carry specific macromolecules such as mRNAs for translation into therapeutic proteins that can target intracellular proteins which mediate disease.
Collections
Subject
Science & Technology
Technology
Nanoscience & Nanotechnology
Materials Science, Biomaterials
Science & Technology - Other Topics
Materials Science
mRNA delivery
cytosolic delivery
polymer nanoparticles
PLA-PEG
macromolecule delivery
CD7
T-ALL
MODIFIED MESSENGER-RNA
PEG-PLA NANOPARTICLES
NUCLEOSIDE MODIFICATIONS
PROTEIN INTERACTIONS
ANTIBODY FRAGMENTS
CATIONIC LIPIDS
IN-VITRO
GENE
CANCER
DOMAIN
Research team
Chromosomal Translocations and Intracellular Antibody Therapeutics
Language
eng
Date accepted
2020-10-29
License start date
2020-12-21
Citation
ACS APPLIED BIO MATERIALS, 2020, 3 (12), pp. 8481 - 8495 (15)
Publisher
AMER CHEMICAL SOC