Application of dual targeting drug delivery system for the improvement of anti-glioma efficacy of doxorubicin
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Zhenliang Sun1,2,*, Xuebing Yan1,*, YiBo Liu3, Linsheng Huang1, Cheng Kong1, Xiao Qu1, Man Wang2, Renyuan Gao1 and Huanlong Qin1
1Department of General Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai 200072, China
2Shanghai Jiaotong University Affiliated Sixth People’s Hospital, South Campus, Shanghai 201499, China
3Longhua Hospital of Shanghai University of TCM, Shanghai 200032, China
*These authors contributed equally to this work
Huanlong Qin, email: firstname.lastname@example.org
Man Wang, email: email@example.com
Keywords: tumor affinity peptide, interleukin-4 receptor, solid tumors, anti-glioma, nanoparticle
Received: February 06, 2017 Accepted: June 17, 2017 Published: July 13, 2017
Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis. Our findings showed that the peptide-functionalized nanoparticles had a high affinity with both tumor cells and vascular endothelial cells. Besides, tumor targeting assay exhibited that AP1 decorated nanoparticles accumulated more in tumor site than the unmodified ones. Moreover, the results of tumor uptake experiments indicated that AP1-NP-DOX might own the ability of blood brain barrier (BBB) penetration. In the anti-glioma study, AP1-NP-DOX exhibited the highest therapeutic effect on tumor-bearing mice compared with the unmodified nanoparticles and free doxorubicin. These results together indicated that AP1-functionalized nanoparticles could represent a promising way to expand the treatment horizons of onco-therapy.
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