pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

Jae-Yoon Shin,1,* Yoosoo Yang,1,* Paul Heo,1 Ji-Chun Lee,1 ByoungJae Kong,1 Jae Youl Cho,1 Keejung Yoon,1 Cheol-Su Shin,2 Jin-Ho Seo,3 Sung-Gun Kim,4 Dae-Hyuk Kweon11Department of Genetic Engineering, College of Biotechnology and Bioengineering, and Center for Human Interface Nano Technology, Sungky...

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Autores principales:	Shin JY, Yang Y, Heo P, Lee JC, Kong BJ, Cho JY, Yoon K, Shin CS, Seo JH, Kim SG, Kweon DH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9bf2f2a0830a453b939a7bf71c6034aa
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spelling	oai:doaj.org-article:9bf2f2a0830a453b939a7bf71c6034aa2021-12-02T03:01:53ZpH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy1176-91141178-2013https://doaj.org/article/9bf2f2a0830a453b939a7bf71c6034aa2012-06-01T00:00:00Zhttp://www.dovepress.com/ph-responsive-high-density-lipoprotein-like-nanoparticles-to-release-p-a10045https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jae-Yoon Shin,1,* Yoosoo Yang,1,* Paul Heo,1 Ji-Chun Lee,1 ByoungJae Kong,1 Jae Youl Cho,1 Keejung Yoon,1 Cheol-Su Shin,2 Jin-Ho Seo,3 Sung-Gun Kim,4 Dae-Hyuk Kweon11Department of Genetic Engineering, College of Biotechnology and Bioengineering, and Center for Human Interface Nano Technology, Sungkyunkwan University, 2APTech Research Center, Suwon, 3Department of Agricultural Biotechnology, Seoul National University, Seoul, 4Department of Biomedical Science, Youngdong University, Chungbuk, South Korea*These authors contributed equally to this workBackground: Nanoparticles undergoing physicochemical changes to release enclosed drugs at acidic pH conditions are promising vehicles for antitumor drug delivery. Among the various drug carriers, high-density lipoprotein (HDL)-like nanoparticles have been shown to be beneficial for cancer chemotherapy, but have not yet been designed to be pH-responsive.Methods and results: In this study, we developed a pH-responsive HDL-like nanoparticle that selectively releases paclitaxel, a model antitumor drug, at acidic pH. While the well known HDL-like nanoparticle containing phospholipids, phosphatidylcholine, and apolipoprotein A-I, as well as paclitaxel (PTX-PL-NP) was structurally robust at a wide range of pH values (3.8&ndash;10.0), the paclitaxel nanoparticle that only contained paclitaxel and apoA-I selectively released paclitaxel into the medium at low pH. The paclitaxel nanoparticle was stable at physiological and basic pH values, and over a wide range of temperatures, which is a required feature for efficient cancer chemotherapy. The homogeneous assembly enabled high paclitaxel loading per nanoparticle, which was 62.2% (w/w). The molar ratio of apolipoprotein A-I and paclitaxel was 1:55, suggesting that a single nanoparticle contained approximately 110 paclitaxel particles in a spherical structure with a 9.2 nm diameter. Among the several reconstitution methods applied, simple dilution following sonication enhanced the reconstitution yield of soluble paclitaxel nanoparticles, which was 0.66. As a result of the pH responsiveness, the anticancer effect of paclitaxel nanoparticles was much more potent than free paclitaxel or PTX-PL-NP.Conclusion: The anticancer efficacy of both paclitaxel nanoparticles and PTX-PL-NP was dependent on the expression of scavenger receptor class B type I, while the killing efficacy of free paclitaxel was independent of this receptor. We speculate that the pH responsiveness of paclitaxel nanoparticles enabled efficient endosomal escape of paclitaxel before lysosomal break down. This is the first report on pH-responsive nanoparticles that do not contain any synthetic polymer.Keywords: pH responsiveness, nanoparticle, apolipoprotein A-I, paclitaxelShin JYYang YHeo PLee JCKong BJCho JYYoon KShin CSSeo JHKim SGKweon DHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2805-2816 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shin JY Yang Y Heo P Lee JC Kong BJ Cho JY Yoon K Shin CS Seo JH Kim SG Kweon DH pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy
description	Jae-Yoon Shin,1,* Yoosoo Yang,1,* Paul Heo,1 Ji-Chun Lee,1 ByoungJae Kong,1 Jae Youl Cho,1 Keejung Yoon,1 Cheol-Su Shin,2 Jin-Ho Seo,3 Sung-Gun Kim,4 Dae-Hyuk Kweon11Department of Genetic Engineering, College of Biotechnology and Bioengineering, and Center for Human Interface Nano Technology, Sungkyunkwan University, 2APTech Research Center, Suwon, 3Department of Agricultural Biotechnology, Seoul National University, Seoul, 4Department of Biomedical Science, Youngdong University, Chungbuk, South Korea*These authors contributed equally to this workBackground: Nanoparticles undergoing physicochemical changes to release enclosed drugs at acidic pH conditions are promising vehicles for antitumor drug delivery. Among the various drug carriers, high-density lipoprotein (HDL)-like nanoparticles have been shown to be beneficial for cancer chemotherapy, but have not yet been designed to be pH-responsive.Methods and results: In this study, we developed a pH-responsive HDL-like nanoparticle that selectively releases paclitaxel, a model antitumor drug, at acidic pH. While the well known HDL-like nanoparticle containing phospholipids, phosphatidylcholine, and apolipoprotein A-I, as well as paclitaxel (PTX-PL-NP) was structurally robust at a wide range of pH values (3.8&ndash;10.0), the paclitaxel nanoparticle that only contained paclitaxel and apoA-I selectively released paclitaxel into the medium at low pH. The paclitaxel nanoparticle was stable at physiological and basic pH values, and over a wide range of temperatures, which is a required feature for efficient cancer chemotherapy. The homogeneous assembly enabled high paclitaxel loading per nanoparticle, which was 62.2% (w/w). The molar ratio of apolipoprotein A-I and paclitaxel was 1:55, suggesting that a single nanoparticle contained approximately 110 paclitaxel particles in a spherical structure with a 9.2 nm diameter. Among the several reconstitution methods applied, simple dilution following sonication enhanced the reconstitution yield of soluble paclitaxel nanoparticles, which was 0.66. As a result of the pH responsiveness, the anticancer effect of paclitaxel nanoparticles was much more potent than free paclitaxel or PTX-PL-NP.Conclusion: The anticancer efficacy of both paclitaxel nanoparticles and PTX-PL-NP was dependent on the expression of scavenger receptor class B type I, while the killing efficacy of free paclitaxel was independent of this receptor. We speculate that the pH responsiveness of paclitaxel nanoparticles enabled efficient endosomal escape of paclitaxel before lysosomal break down. This is the first report on pH-responsive nanoparticles that do not contain any synthetic polymer.Keywords: pH responsiveness, nanoparticle, apolipoprotein A-I, paclitaxel
format	article
author	Shin JY Yang Y Heo P Lee JC Kong BJ Cho JY Yoon K Shin CS Seo JH Kim SG Kweon DH
author_facet	Shin JY Yang Y Heo P Lee JC Kong BJ Cho JY Yoon K Shin CS Seo JH Kim SG Kweon DH
author_sort	Shin JY
title	pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy
title_short	pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy
title_full	pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy
title_fullStr	pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy
title_full_unstemmed	pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy
title_sort	ph-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic ph in cancer chemotherapy
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/9bf2f2a0830a453b939a7bf71c6034aa
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pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

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