A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model
- Authors
- Tan, Xiaonan; Kim, Gyeungyun; Lee, Dahee; Oh, Jungju; Kim, Minkyung; Piao, Chunxian; Lee, Jaewon; Lee, Min Sang; Jeong, Ji Hoon; Lee, Minhyung
- Issue Date
- Feb-2018
- Publisher
- ROYAL SOC CHEMISTRY
- Citation
- BIOMATERIALS SCIENCE, v.6, no.2, pp.407 - 417
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMATERIALS SCIENCE
- Volume
- 6
- Number
- 2
- Start Page
- 407
- End Page
- 417
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4737
- DOI
- 10.1039/c7bm01088e
- ISSN
- 2047-4830
- Abstract
- A glioblastoma is a common primary brain tumor that expresses microRNA- 21 (miR-21), which inhibits the expression of pro-apoptotic genes such as phosphatase and tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic effects for glioblastomas. In this study, curcumin was loaded into deoxycholic acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle (DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and miR21ASO. Gel retardation and heparin competition assays showed that DP-Cur formed stable complexes with miR21ASO. The anti-tumor effects of the combined delivery of curcumin and miR21ASO were evaluated in C6 glioblastoma cells. In vitro transfection showed that DP-Cur had an miR21ASO delivery efficiency similar to that of polyethylenimine (25 kDa, PEI25k) and DP. In the C6 cells, the delivery of miR21ASO using DP-Cur effectively reduced the miR21 level. The miR21ASO/DP-Cur complex induced apoptosis more effectively than the single delivery of curcumin or miR21ASO. The therapeutic effect of the miR21ASO/DP-Cur complex was also evaluated in an intracranial glioblastoma animal model. The miR21ASO/DP-Cur complex reduced the tumor volume more effectively than single therapy of curcumin or miR21ASO. Immunohistochemistry showed that PDCD4 and PTEN were induced in the miR21ASO/DP and miR21ASO/DP-Cur complex groups. Therefore, DP-Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and curcumin may be useful in the development of combination therapy for glioblastoma.
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