A hematoporphyrin-based delivery system for drug resistance reversal and tumor ablation.

Abstract

Nanotechnology-based drug delivery systems have been intensively investigated, while only a few of them can be used for clinic application. Hematoporphyrin (HP), a major molecule in erythrocyte, has been widely used in photodynamic therapy (PDT). In the present study, polyethylene glycol (PEG) modified hematoporphyrin (HPP)-based nanoparticle system was designed to load doxorubicin (HPPD), in achieving a synergistic effect of chemotherapy and PDT. Herein we presented that HPPD formed narrowly dispersed nanoparticles at 35 ± 2 nm, yielding an enhanced drug release at pH5.8 along with laser radiation. This combined treatment with HPPD and radiation facilitated drug penetration to the nucleus thereby reducing 12-fold decrease in IC50 value and promoting apoptosis in drug-resistant breast cancer cells. Notably, little toxicity was detected with HPP at the cellular level and in animal models. Live animal imaging revealed that HPPD performed ultra high tumor uptake in both mice and marmoset models. Strikingly, intravenous administration of HPPD and radiation on the tumor achieved efficient tumor ablation, without inducing myocardial injury. We report here the development of a biomolecule, HP-based nanoparticle system, which can synergistically yield chemotherapy and PDT.

• Authors: Yu Ren, Ruirui Wang, Yang Liu, Hua Guo, Xuan Zhou, Xubo Yuan, Chaoyong Liu, Jianguo Tian, Haifang Yin, Yinsong Wang, Ning Zhang
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 8 Pg. 2462-70 (Mar 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24373420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Drug Carriers
• Hematoporphyrins
• Polyethylene Glycols
• Doxorubicin
• L-Lactate Dehydrogenase
• Creatine Kinase

Topics

• Administration, Intravenous
• Animals
• Apoptosis (drug effects)
• Callithrix
• Cell Survival
• Creatine Kinase (blood)
• Disease Models, Animal
• Doxorubicin (pharmacology)
• Drug Carriers (chemistry)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Hematoporphyrins (chemistry)
• Humans
• Hydrogen-Ion Concentration
• Inhibitory Concentration 50
• L-Lactate Dehydrogenase (blood)
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (chemistry)
• Photochemotherapy (methods)
• Polyethylene Glycols (chemistry)