RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cellsopen access
- Authors
- Lee, Sang Gon; Kim, Chang Hyun; Sung, Si Woo; Lee, Eun Seok; Goh, Min Su; Yoon, Ho Yub; Kang, Myung Joo; Lee, Sangkil; Choi, Young Wook
- Issue Date
- Jun-2018
- Publisher
- DOVE MEDICAL PRESS LTD
- Keywords
- nanostructured lipid carriers; RIPL peptide; intracellular delivery; docetaxel; antitumor efficacy; targeting
- Citation
- INTERNATIONAL JOURNAL OF NANOMEDICINE, v.13, pp 3263 - 3278
- Pages
- 16
- Journal Title
- INTERNATIONAL JOURNAL OF NANOMEDICINE
- Volume
- 13
- Start Page
- 3263
- End Page
- 3278
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/1491
- DOI
- 10.2147/IJN.S166021
- ISSN
- 1178-2013
1178-2013
- Abstract
- Background: To facilitate selective and enhanced drug delivery to hepsin (Hpn)-expressing cancer cells, RIPL peptide (IPLVVPLRRRRRRRRC, 16-mer)-conjugated nanostructured lipid carriers (RIPL-NLCs) were developed. Methods: NLCs were prepared using a solvent emulsification-evaporation method and the RIPL peptide was conjugated to the maleimide-derivatized NLCs via the thiol-maleimide reaction. Employing a fluorescent probe (DiI), in vitro target-selective intracellular uptake behaviors were observed using fluorescence microscopy and flow cytometry. Separately, docetaxel (DTX) was encapsulated by pre-loading technique, then cytotoxicity and drug release were evaluated. In vivo antitumor efficacy was investigated in BALB/c nude mice with SKOV3 cell tumors after intratumoral injections of different DTX formulations at a dose equivalent to 10 mg/kg DTX. Results: RIPL-NLCs showed positively charged nanodispersion, whereas NLCs were negatively charged. DTX was successfully encapsulated with an encapsulation efficiency and drug loading capacity of 95-98% and 44-46 mu g/mg, respectively. DTX release was diffusion-controlled, revealing the best fit to the Higuchi equation. Cellular uptake of DiI-loaded RIPL-NLCs was 8.3-and 6.2-fold higher than that of DiI-loaded NLCs, in Hpn(+) SKOV3 and LNCaP cells, respectively. The translocation of RIPL-NLCs into SKOV3 cells was time-dependent with internalization within 1 h and distribution throughout the cytoplasm after 2 h. DTX-loaded RIPL-NLCs (DTX-RIPL-NLCs) revealed dose-dependent in vitro cytotoxicity, while drug-free formulations were non-cytotoxic. In SKOV3-bearing xenograft mouse model, DTX-RIPL-NLCs significantly inhibited tumor growth: the inhibition ratios of the DTX solution-treated and DTX-RIPL-NLC-treated groups were 61.4% and 91.2%, respectively, compared to those of the saline-treated group (control). Conclusion: RIPL-NLCs are good candidates for Hpn-selective drug targeting with a high loading capacity of hydrophobic drug molecules.
- Files in This Item
-
- Appears in
Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/1491)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.