Multicompartment micelle-structured peptide nanoparticles: A new biocompatible gene- and drug-delivery tool

Self‐assembled, biodegradable materials that embed fragile, soluble, or insoluble compounds of therapeutic interest have potential use as drug delivery systems. The bead‐forming peptide Ac‐X3‐gT can embed hydrophobic and hydrophilic payloads. Loaded peptide beads were internalized by human acute monocytic leukemia cell line (THP‐1) macrophages, THP‐1 monocytes, and hepatocellular carcinoma cells (Huh7). Furthermore, paclitaxel and doxorubicin coencapsulated in the peptide beads were delivered to THP‐1 monocytes, causing a decrease in cell viability due to the activity of the anticancer drugs. In addition to the bead‐forming peptide Ac‐X3‐gT, the use of a positively charged peptide analogue increased the RNA/DNA embedding efficiency to 99% by charge compensation and micellar complexation. Internalization of the resulting gene delivery systems by Huh7 cells led to specific gene silencing either by embedded small interfering RNA or by plasmid‐encoding small hairpin RNA delivered in cells. The new class of purely peptidic material caused no measurable toxicity during in vitro experiments, thereby indicating potential use as a drug delivery system for multidrug delivery and gene therapy. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1155–1163, 2014.