Dendron micelles have shown promising results as a multifunctional delivery system, owing to their unique molecular architecture. Herein, we have prepared a novel poly(amidoamine) (PAMAM) dendron-lipid hybrid nanoparticle (DLNP) as a nanocarrier for drug/gene co-delivery and examined how the dendron generation of DLNPs impacts their cargo-carrying capabilities. DLNPs, formed by a thin-layer hydration method, were internally loaded with chemo-drugs and externally complexed with plasmids. Compared to generation 2 dendron DLNP (D2LNPs), D3LNPs demonstrated a higher drug encapsulation efficiency (31% vs 87%) and better gene complexation (minimal N/P ratio of 20:1 vs 5:1 for complexation) due to their smaller micellar aggregation number and higher charge density, respectively. Furthermore, D3LNPs were able to avoid endocytosis and subsequent lysosomal degradation and demonstrated a higher cellular uptake than D2LNPs. As a result, D3LNPs exhibited significantly enhanced antitumor and gene transfection efficacy in comparison to D2LNPs. These findings provide design cues for engineering multifunctional dendron-based nanotherapeutic systems for effective combination cancer treatment.
|Number of pages||10|
|Publication status||Published - 2021 Sept 13|
Bibliographical noteFunding Information:
The authors thank Drs. HongY. Cho and Sin-jung Park for performing earlier experiments in this study. This study was partially supported by NSF under the grant numbers DMR-1808251 and DMR-1741560 and by Milton J. Henrichs Endowed Chair fund. This research was also supported in part by the University of Wisconsin Head and Neck SPORE grant (P50DE026787).
© 2021 American Chemical Society
All Science Journal Classification (ASJC) codes
- Polymers and Plastics
- Materials Chemistry