Peptide-Tunable Drug Cytotoxicity via One-Step Assembled Polymer Nanoparticles

摘要

The delivery of therapeutics into cells is important for biomed-ical applications ranging from gene therapy to drug delivery. Since the commercial introduction of Doxil~®, particle-based drug carriers have been used to improve therapeutic outcomes. Carriers are useful for transporting drugs to cells and reducing the non-specific toxicity of the drug, while cocktails of therapeutics are receiving intense study for enhancing the specific desired toxicity. The combination of a non-toxic facilitating molecule with specific therapeutics has proven to be especially useful for promoting enhanced cellular responses. Cell penetrating peptides (CPPs) are a useful class of facilitator molecules that have found application in imaging, and gene and drug delivery. A particularly interesting CPP is the non-toxic arginine-rich trans-activating transcriptional activator (Tat) and the corresponding engineered derivatives. These CPPs have been used to enhance cellular uptake, endosomal escape and/or nuclear targeting to facilitate improved therapeutic responses.