Improved Protein Toxin Delivery Based on ATTEMPTS Systems.

Improved Protein Toxin Delivery Based on ATTEMPTS Systems. Curr Drug Targets. 2017 Mar 01;: Authors: Huang Y, Yang VC, Li F, Shin MC, Wang H, Min KA, Zhang M, Chen Y Abstract Ribosome-inactivating proteins (RIPs) are wildly found in multiple species of plants, bacteria and fungi. As a special family of protein toxins, RIPs can inhibit protein synthesis and induce cell death via inactivating ribosome in eukaryotic cells. Thus, RIPs have been applied for anti-tumor therapy in the past two decades. However, because of poor cell permeability, nonselective mode of action for tumor cells, poor pharmacokinetic profiles and immunogenicity, their clinical application has been severely constrained. As an effort to overcome these obstacles, tumor-specific monoclonal antibodies (mAb) have been conjugated to RIPs (forming so called "immunotoxins") specifically to increase their cytotoxicity and provide tumor targeting. Nevertheless, immunotoxins yet have not fully resolved all the issues and, remains still critical challenges, such as immunogenicity and inability to penetrate into the deep site of tumor. Hence, a novel cell-penetrating peptide (CPP)-modified ATTEMPTS system based on combination of CPP-mediated penetration and antibody-mediated tumor targeting, with triggerable drug release function, was developed to achieve effective and safe delivery of protein toxin. PMID: 28260497 [PubMed - as supplied by publisher]
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research