title: Twin-Arginine Translocation Peptide Conjugated Epirubicin-Loaded Nanoparticles for Enhanced Tumor Penetrating and Targeting.
abstract: One major obstacle in the application of drug delivery systems for cancer chemotherapy is their poor penetration in tumor tissues. Conjugating active ligand moieties to the surface of nanoparticles may be a promising approach for enhancing the tumor accumulation and penetration of nanoparticles. Herein, the cell-penetrating peptide twin-arginine translocation (Tat)-conjugated epirubicin-loaded poly(lactic-glycolic acid) nanoparticles were prepared to achieve deep tumor penetration. The morphology and size of nanoparticles were characterized by scanning electron microscopy and dynamic light scattering, and the biological behaviors of nanoparticles were evaluated. It is demonstrated that Tat-conjugated nanoparticles have a significant improvement in antitumor activity and biodistribution compared with nonconjugated nanoparticles. Importantly, Tat conjugated on the surface of nanoparticles could facilitate the encapsulated drug penetration into deeper tumor tissue. Additionally, Tat-conjugated nanoparticles have good biocompatibility, as demonstrated by hemolytic tests, in vitro cytotoxicity, and histology study. These results suggested that the Tat-conjugated nanoparticles, as a powerful delivery system for chemotherapeutic drug, would have a promising application in human cancer therapy.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China; Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Luzhong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Guicai
authors.initials: G
authors.lastname: Li
authors.affiliation: Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: zhouyoulang@ntu.edu.cn.
authors.forename: Youlang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: yangym@ntu.edu.cn.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D015251:Epirubicin / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution / Q000502:physiology; D000069294:Twin-Arginine-Translocation System / Q000494:pharmacology*
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D000069294:Twin-Arginine-Translocation System; D015251:Epirubicin; D001120:Arginine
keywords: Tat peptide; conjugaton; controlled release; drug delivery; epirubicin; nanoparticle; poly(lactic/glycolic) acid; tumor penetration