title: Multifunctional nanocarrier mediated co-delivery of doxorubicin and siRNA for synergistic enhancement of glioma apoptosis in rat.
abstract: As the most fatal malignancy in brain, glioma cannot be effectively treated with the conventional chemotherapy and thus techniques which may improve the chemotherapeutic effect are of great importance in clinical glioma treatment. Based on the folate-targeted multifunctional nanocarrier developed in our lab, effective co-delivery of DOX and siRNA into rat C6 glioma cells over-expressing folate receptors was achieved. Although cell apoptosis was initiated even at low DOX doses such as 0.5 μg/mL in the DOX-alone treatment mediated by the folate-targeted nanocarrier, anti-apoptotic response in C6 cells was activated as well, as revealed by molecular biological investigations. Delivery of BCL-2 siRNA using the folate-targeted nanocarrier can effectively suppress the anti-apoptotic response and sensitized C6 cells to DOX treatment both in vitro and in vivo. In particular, animal studies using the in situ rat C6 glioma model showed that the folate-targeted co-delivery of BCL-2 siRNA and DOX caused not only an obvious down-regulation of the anti-apoptotic BCL-2 gene but also a remarkable up-regulation of the pro-apoptotic Bax gene, resulting in the significantly elevated level of caspase-3 activation and remarkable cell apoptosis in tumor tissues. Our results strongly demonstrated the synergistic effect of siRNA and DOX in inducing glioma C6 cell apoptosis, upon which an excellent therapeutic effect was achieved using the folate-targeted co-delivery strategy as indicated by the effective tumor growth inhibition and prolonged rat survival time in the animal test.
authors: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors: Du
authors: D
authors: Cheng
authors: Nuo
authors: N
authors: Cao
authors: Jifeng
authors: J
authors: Chen
authors: Xingsu
authors: X
authors: Yu
authors: Xintao
authors: X
authors: Shuai
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D004357:Drug Synergism; D020868:Gene Silencing; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D004317:Doxorubicin