Abstract
Co-delivery of antigen-encoding plasmid DNA (pDNA) and immune-modulatory molecules has importance in advancing gene-based immunotherapy and vaccines. Here novel star polymer nanocarriers were synthesized for co-delivery of pDNA and imiquimod (IMQ), a poorly soluble small-molecule adjuvant, to dendritic cells. Computational modeling and experimental results revealed that the polymers formed either multimolecular or unimolecular core-shell-type micelles in water, depending on the nature of the outer hydrophilic shell. Micelles loaded with both IMQ and pDNA were able to release IMQ in response to intracellular pH of the endo-lysosome and transfect mouse dendritic cells (DC2.4 line) in vitro. Importantly, IMQ-loaded micelle/pDNA complexes displayed much enhanced transfection efficiency than IMQ-free complexes. These results demonstrate the feasibility of co-delivery of pDNA and IMQ to antigen-presenting cells by multifunctional polymer nanocarriers with potential use in gene-based vaccine approaches.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 378-389 |
| Number of pages | 12 |
| Journal | Acta Biomaterialia |
| Volume | 48 |
| DOIs | |
| State | Published - Jan 15 2017 |
Bibliographical note
Funding Information:Partial support of this project was provided through discretionary funds from the University of Minnesota (to CW). LZ acknowledges grants from the National Natural Science Foundation of China (No. 91434125), Team Project of Natural Science Foundation of Guangdong Province, China (No. S2011030001366), and Science and Technology Foundation of Guangdong Province (No. 2015B020237008). WL thanks the China Scholarship Council (CSC) (No. 201406150021) for a fellowship to support her 1-year stay at the University of Minnesota.
Publisher Copyright:
© 2016 Acta Materialia Inc.
Keywords
- Co-delivery
- DNA delivery
- Imiquimod
- Micelles
- Star copolymer
