방사선의학 웹진

바로가기  >

(a) polyglycerol nanoemulsion (pg-NE)에 folate를 도입하여 제조된 fpg-NE 구조식

(b) polyethylenglycol에 folate를 도입하여 제조한 fpeg-NE의 구조식

(c) Nanoemulsion을 처리한 HeLa cell의 confocal fluorescence microscopic images ( peg-pNE, pg-pNE, fpeg-pNE-1, fpeg-pNE-2, and fpg-pNE containing fluorescein-PCL (green) and BODIPY® -paclitaxel (red). Scale bars = 10 μm).

Abstract
Despite the excellent biocompatibility and antifouling effect of poly(ethylene glycol) (PEG), the high steric hindrance, limited chemical functionality, and low ligand multivalency of PEGylated nanocarriers often lead to inefficient cell targeting and intracellular trafficking. Hence, a new structure of hydrophilic corona allowing a higher ligand density without loss of excellent biocompatibility is highly desirable. Here we introduce tumor-targeted polyglycerolated (PGylated) nanocarriers that dramatically enhance the in vivo therapeutic efficacy of incorporated paclitaxel simply by increasing the surface density of hydrophobic tumor-targeting ligands. Linear polyglycerol-poly (ε-caprolactone) block copolymer (PG-b-PCL) is used to prepare PGylated lipiodol nanoemulsions, where PG serves as a corona conjugated with a large number of folic acid (FA) for efficient tumor targeting. Unlike FA-PEGylated nanoemulsions, FA-PGylated nanoemulsions can display a larger number of FA without structural destabilization. This property enables excellent anti-cancer activities and effective tumor regression in a cervical cancer xenograft murine model at a cumulative drug dose of ∼5 mg kg-1, which is about four fold smaller than that of commercial Taxol formulation. This study highlights the importance of surface chemistry of nanocarriers that enable multivalent ligand functionalization and high tolerance to the conjugation of hydrophobic ligands, which make PG as a very effective hydrophilic corona for in vivo drug delivery.

Author information

Le Kim TH1, Yu JH1, Jun H1, Yang MY2, Yang MJ3, Cho JW3, Kim JW4, Kim JS5, Nam YS6.
1
Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
2
KAIST Institute for the NanoCentury, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
3
Pathology Research Group, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, 30 Baekhak 1-gil, Jeongeup, Jeonbuk, 56212, Republic of Korea.
4
Department of Bionano Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 426-791, Republic of Korea; Department of Chemical and Molecular Engineering, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea. Electronic address: kjwoong@hanyang.ac.kr.
5
Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. Electronic address: eliekim@kaist.ac.kr.
6
Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea; KAIST Institute for the NanoCentury, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. Electronic address: yoonsung@kaist.ac.kr.