Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system.

Abstract

The study investigated the reversal of multidrug resistance (MDR) and the biodistribution of nanoparticles (NPs) that target leukemia cells in a nude mice model via a surface-bound transferrin (Tf). The cytotoxic cargo of daunorubicin (DNR) and tetrandrine (Tet) was protected in the NPs by an outer coat composed of polyethylene glycol (PEG)-poly-L-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) NPs. Injection of DNR-Tet-Tf-PEG-PLL-PLGA NPs into nude mice bearing MDR leukemia cell K562/A02 xenografts was shown to inhibit tumor growth, and contemporaneous immunohistochemical analysis of tumor tissue showed the targeted NPs induced apoptosis in tumor cells. Targeted tumor cells exhibited a marked increase in Tf receptor expression, with noticeable decreases in P-glycoprotein, MDR protein, and nuclear factor κB, as assessed by quantitative real-time polymerase chain reaction and Western blot analysis. Moreover, the concentration of DNR was shown to increase in plasma, tumor tissue, and major organs. Flow cytometry analysis with a near-infrared fluorescent (NIRF) dye, NIR797, was used to study the effectiveness of Tf as a targeting group for leukemia cells, a finding that was supported by NIRF imaging in tumor-bearing nude mice. In summary, our studies show that DNR-Tet-Tf-PEG-PLL-PLGA NPs provide a specific and effective means to target cytotoxic drugs to MDR tumor cells.

• Authors: Liting Guo, Haijun Zhang, Fei Wang, Ping Liu, Yonglu Wang, Guohua Xia, Ran Liu, Xueming Li, Haixiang Yin, Hulin Jiang, Baoan Chen
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 10 Pg. 4535-47 ( 2015) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 26213467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Polyesters
• monomethoxy (polyethylene glycol)-poly(lactide-co-glycolide)-poly(lysine)
• Polylysine
• Polyethylene Glycols

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Drug Carriers (chemistry, pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Mice
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Polylysine (analogs & derivatives, chemistry)
• Xenograft Model Antitumor Assays