title: Multicompartment micelle-structured peptide nanoparticles: a new biocompatible gene- and drug-delivery tool.
abstract: 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.
authors: Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056, Basel, Switzerland.
authors: Dirk
authors: D
authors: de Bruyn Ouboter
authors: Thomas
authors: T
authors: Schuster
authors: Vijay
authors: V
authors: Shanker
authors: Markus
authors: M
authors: Heim
authors: Wolfgang
authors: W
authors: Meier
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D002232:Carbocyanines / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008823:Micelles; D008863:Microspheres; D053758:Nanoparticles / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D002232:Carbocyanines; D008823:Micelles; D010455:Peptides; D034741:RNA, Small Interfering; C089187:cyanine dye 3
keywords: drug delivery system; formulation; gene therapy; peptidic amphiphiles; self-assembly