RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells

Sang Gon Lee,1,* Chang Hyun Kim,1,* Si Woo Sung,1 Eun Seok Lee,1 Min Su Goh,1 Ho Yub Yoon,1 Myung Joo Kang,2 Sangkil Lee,3 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2College of Pharmacy, Dankook University, Chungnam, Republic of Korea; 3College of Pharma...

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Autores principales:	Lee SG, Kim CH, Sung SW, Lee ES, Goh MS, Yoon HY, Kang MJ, Lee S, Choi YW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Nanostructured lipid carriers RIPL peptide Intracellular delivery Docetaxel Antitumor efficacy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7b5808a315834c318026f81c69e89db0
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spelling	oai:doaj.org-article:7b5808a315834c318026f81c69e89db02021-12-02T05:23:49ZRIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells1178-2013https://doaj.org/article/7b5808a315834c318026f81c69e89db02018-06-01T00:00:00Zhttps://www.dovepress.com/ripl-peptide-conjugated-nanostructured-lipid-carriers-for-enhanced-int-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sang Gon Lee,1,* Chang Hyun Kim,1,* Si Woo Sung,1 Eun Seok Lee,1 Min Su Goh,1 Ho Yub Yoon,1 Myung Joo Kang,2 Sangkil Lee,3 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2College of Pharmacy, Dankook University, Chungnam, Republic of Korea; 3College of Pharmacy, Keimyung University, Daegu, Republic of Korea *These authors contributed equally to this work 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 µg/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. Keywords: nanostructured lipid carriers, RIPL peptide, intracellular delivery, docetaxel, antitumor efficacy, targetingLee SGKim CHSung SWLee ESGoh MSYoon HYKang MJLee SChoi YWDove Medical PressarticleNanostructured lipid carriersRIPL peptideIntracellular deliveryDocetaxelAntitumor efficacyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3263-3278 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nanostructured lipid carriers RIPL peptide Intracellular delivery Docetaxel Antitumor efficacy Medicine (General) R5-920
spellingShingle	Nanostructured lipid carriers RIPL peptide Intracellular delivery Docetaxel Antitumor efficacy Medicine (General) R5-920 Lee SG Kim CH Sung SW Lee ES Goh MS Yoon HY Kang MJ Lee S Choi YW RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells
description	Sang Gon Lee,1,* Chang Hyun Kim,1,* Si Woo Sung,1 Eun Seok Lee,1 Min Su Goh,1 Ho Yub Yoon,1 Myung Joo Kang,2 Sangkil Lee,3 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2College of Pharmacy, Dankook University, Chungnam, Republic of Korea; 3College of Pharmacy, Keimyung University, Daegu, Republic of Korea *These authors contributed equally to this work 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 µg/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. Keywords: nanostructured lipid carriers, RIPL peptide, intracellular delivery, docetaxel, antitumor efficacy, targeting
format	article
author	Lee SG Kim CH Sung SW Lee ES Goh MS Yoon HY Kang MJ Lee S Choi YW
author_facet	Lee SG Kim CH Sung SW Lee ES Goh MS Yoon HY Kang MJ Lee S Choi YW
author_sort	Lee SG
title	RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells
title_short	RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells
title_full	RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells
title_fullStr	RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells
title_full_unstemmed	RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells
title_sort	ripl peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/7b5808a315834c318026f81c69e89db0
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RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells

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