Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 104, Issue 12, Pages 4185-4196Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.24649
Keywords
Tat peptide; conjugaton; nanoparticle; drug delivery; poly(lactic/glycolic) acid; epirubicin; controlled release; tumor penetration
Funding
- Natural Science Foundation of Jiangsu Province of China [BK20130390, BK20140429]
- National High Technology Research and Development Program of China [2012AA020502]
- National Natural Science Foundation of China [81171457, 81371687, 81401796]
- Natural Science Research Program of Jiangsu Education Department [13KJB310014]
- Priority of Academic Program Development of Jiangsu Higher Education Institutions
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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. (C) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association
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