Transferrin modified PEG-PLA-resveratrol conjugates: in vitro and in vivo studies for glioma.
Glioblastoma is one of the most malignant brain tumors with a poor prognosis. In this study, we examined the effects of transferrin (Tf)-modified poly ethyleneglycol-poly lactic acid (PEG-PLA) nanoparticles conjugated with resveratrol (Tf-PEG-PLA-RSV) to glioma therapy in vitro and in vivo. The cell viability of Tf-PEG-PLA-RSV on C6 and U87 glioma cells was determined by the MTT assay. In vivo biodistribution and antitumor activity were investigated in Brain glioma bearing rat model of C6 glioma by i.p. administration of RSV-polymer conjugates. We found that the average diameter of each Tf-PEG-PLA-RSV is around 150 nm with 32 molecules of Tf on surface. In vitro cytotoxicity of PEG-PLA-RSV against C6 and U87 cells was higher than that of free RSV, and further the modification of Tf enhanced the cytotoxicity of the RSV-polymer conjugates as a result of the increased cellular uptake of the RSV-modified conjugates by glioma cells. In comparison with free RSV, RSV conjugates could significantly decrease tumor volume and accumulate in brain tumor, which resulted in prolonging the survival of C6 glioma-bearing rats. These results suggest that Tf-NP-RSV had a potential of therapeutic effect to glioma both in vitro and in vivo and might be a potential candidate for targeted therapy of glioma and worthy of further investigation.
Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of NanJing University, Zhongshan Road, Nanjing 210008, China.
Wanhua
W
Guo
Aimei
A
Li
Zhijun
Z
Jia
Yi
Y
Yuan
Haifeng
H
Dai
Hongxiu
H
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D016019:Survival Analysis; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D013267:Stilbenes; D014168:Transferrin; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D000077185:Resveratrol
Glioma; In vitro and in vivo; PEG-PLA; Resveratrol; Transferrin