期刊
BIOMACROMOLECULES
卷 22, 期 9, 页码 3746-3755出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.1c00541
关键词
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资金
- NSF [DMR-1808251, DMR-1741560]
- Milton J. Henrichs Endowed Chair fund
- University of Wisconsin Head and Neck SPORE grant [P50DE026787]
Dendron micelles have been used as a promising multifunctional delivery system due to their unique molecular structure. A novel poly(amidoamine) dendron-lipid hybrid nanoparticle (DLNP) was prepared as a nanocarrier for drug/gene co-delivery, with generation 3 DLNPs showing higher drug encapsulation efficiency and better gene complexation compared to generation 2 DLNPs. Additionally, D3LNPs were able to avoid endocytosis and lysosomal degradation, leading to increased cellular uptake and enhanced antitumor and gene transfection efficacy.
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.
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