Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model

Thais Leite Nascimento; Hervé Hillaireau; Juliette Vergnaud; Melania Rivano; Claudine Deloménie; Delphine Courilleau; Silvia Arpicco; Jung Soo Suk; Justin Hanes; Elias Fattal

doi:10.1016/j.ijpharm.2016.06.125

Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model

Thais Leite Nascimento, Hervé Hillaireau, Juliette Vergnaud, Melania Rivano, Claudine Deloménie, Delphine Courilleau, Silvia Arpicco, Jung Soo Suk, Justin Hanes, Elias Fattal

School of Medicine

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

We have investigated the impact of hyaluronic acid (HA)-coating on the targeting capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake and localization of HA-lipoplexes were evaluated by flow cytometry and fluorescence microscopy and both methods showed that these lipoplexes were rapidly internalized and localized primarily within the cytoplasm. Inhibition of luciferase expression on the A549-luciferase lung cancer cell line was achieved in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition was obtained in vitro with HA-lipoplexes at +/− ratio 2. In vivo, in a murine A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti-luciferase siRNA led to a statistically significant decrease of luciferase expression as opposed to progressive increase with non-modified lipoplexes or NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice treated with HA-lipoplexes supported the inhibition effect due to siRNA. These results highlight the potential of HA-lipoplexes in CD44-targeting siRNA delivery.

Original language	English (US)
Pages (from-to)	103-111
Number of pages	9
Journal	International Journal of Pharmaceutics
Volume	514
Issue number	1
DOIs	https://doi.org/10.1016/j.ijpharm.2016.06.125
State	Published - Nov 30 2016

Keywords

A549
CD44
Hyaluronic acid
Lipoplexes
Luciferase
siRNA

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.ijpharm.2016.06.125

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title = "Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model",

abstract = "We have investigated the impact of hyaluronic acid (HA)-coating on the targeting capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake and localization of HA-lipoplexes were evaluated by flow cytometry and fluorescence microscopy and both methods showed that these lipoplexes were rapidly internalized and localized primarily within the cytoplasm. Inhibition of luciferase expression on the A549-luciferase lung cancer cell line was achieved in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition was obtained in vitro with HA-lipoplexes at +/− ratio 2. In vivo, in a murine A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti-luciferase siRNA led to a statistically significant decrease of luciferase expression as opposed to progressive increase with non-modified lipoplexes or NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice treated with HA-lipoplexes supported the inhibition effect due to siRNA. These results highlight the potential of HA-lipoplexes in CD44-targeting siRNA delivery.",

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author = "{Leite Nascimento}, Thais and Herv{\'e} Hillaireau and Juliette Vergnaud and Melania Rivano and Claudine Delom{\'e}nie and Delphine Courilleau and Silvia Arpicco and Suk, {Jung Soo} and Justin Hanes and Elias Fattal",

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year = "2016",

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doi = "10.1016/j.ijpharm.2016.06.125",

language = "English (US)",

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AU - Leite Nascimento, Thais

AU - Hillaireau, Hervé

AU - Vergnaud, Juliette

AU - Rivano, Melania

AU - Deloménie, Claudine

AU - Courilleau, Delphine

AU - Arpicco, Silvia

AU - Suk, Jung Soo

AU - Hanes, Justin

AU - Fattal, Elias

PY - 2016/11/30

Y1 - 2016/11/30

N2 - We have investigated the impact of hyaluronic acid (HA)-coating on the targeting capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake and localization of HA-lipoplexes were evaluated by flow cytometry and fluorescence microscopy and both methods showed that these lipoplexes were rapidly internalized and localized primarily within the cytoplasm. Inhibition of luciferase expression on the A549-luciferase lung cancer cell line was achieved in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition was obtained in vitro with HA-lipoplexes at +/− ratio 2. In vivo, in a murine A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti-luciferase siRNA led to a statistically significant decrease of luciferase expression as opposed to progressive increase with non-modified lipoplexes or NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice treated with HA-lipoplexes supported the inhibition effect due to siRNA. These results highlight the potential of HA-lipoplexes in CD44-targeting siRNA delivery.

AB - We have investigated the impact of hyaluronic acid (HA)-coating on the targeting capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake and localization of HA-lipoplexes were evaluated by flow cytometry and fluorescence microscopy and both methods showed that these lipoplexes were rapidly internalized and localized primarily within the cytoplasm. Inhibition of luciferase expression on the A549-luciferase lung cancer cell line was achieved in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition was obtained in vitro with HA-lipoplexes at +/− ratio 2. In vivo, in a murine A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti-luciferase siRNA led to a statistically significant decrease of luciferase expression as opposed to progressive increase with non-modified lipoplexes or NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice treated with HA-lipoplexes supported the inhibition effect due to siRNA. These results highlight the potential of HA-lipoplexes in CD44-targeting siRNA delivery.

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Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model

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