Self-assembled nanoparticles comprising aptide-SN38 conjugates for use in targeted cancer therapy

Hyungjun Kim; Yonghyun Lee; Sukmo Kang; Minsuk Choi; Soyoung Lee; Sunghyun Kim; Vipul Gujrati; Jinjoo Kim; Sangyong Jon

doi:10.1088/0957-4484/27/48/48LT01

Self-assembled nanoparticles comprising aptide-SN38 conjugates for use in targeted cancer therapy

Hyungjun Kim, Yonghyun Lee, Sukmo Kang, Minsuk Choi, Soyoung Lee, Sunghyun Kim, Vipul Gujrati, Jinjoo Kim, Sangyong Jon

Department of Pharmaceutical Sciences

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

18 Scopus citations

Abstract

Self-assembled nanoparticles (NPs) have been intensively utilized as cancer drug delivery carriers because hydrophobic anticancer drugs may be efficiently loaded into the particle cores. In this study, we synthesized and evaluated the therapeutic index of self-assembled NPs chemically conjugated to a fibronectin extra domain B-specific peptide (APT_EDB) and an anticancer agent SN38. The APT_EDB-SN38 formed self-assembled structures with a diameter of 58 ± 3 nm in an aqueous solution and displayed excellent drug loading, solubility, and stability properties. A pharmacokinetic study revealed that the blood circulation half-life of SN38 following injection of the APT_EDB-SN38 NPs was markedly higher than that of the small molecule CPT-11. The APT_EDB-SN38 NPs delivered SN38 to tumor sites by both passive and active targeting. Finally, the APT_EDB-SN38 NPs exhibited potent antitumor activities and low toxicities against EDB-expressing tumors (LLC, U87MG) in mice. This system merits further preclinical and clinical investigations for SN38 delivery.

Original language	English
Article number	48LT01
Journal	Nanotechnology
Volume	27
Issue number	48
DOIs	https://doi.org/10.1088/0957-4484/27/48/48LT01
State	Published - 2 Nov 2016

Bibliographical note

Publisher Copyright:
© 2016 IOP Publishing Ltd.

Keywords

SN38
aptides
cancer therapy
extra domain B of fibronectin
self-assembled nanoparticles

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10.1088/0957-4484/27/48/48LT01

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title = "Self-assembled nanoparticles comprising aptide-SN38 conjugates for use in targeted cancer therapy",

abstract = "Self-assembled nanoparticles (NPs) have been intensively utilized as cancer drug delivery carriers because hydrophobic anticancer drugs may be efficiently loaded into the particle cores. In this study, we synthesized and evaluated the therapeutic index of self-assembled NPs chemically conjugated to a fibronectin extra domain B-specific peptide (APTEDB) and an anticancer agent SN38. The APTEDB-SN38 formed self-assembled structures with a diameter of 58 ± 3 nm in an aqueous solution and displayed excellent drug loading, solubility, and stability properties. A pharmacokinetic study revealed that the blood circulation half-life of SN38 following injection of the APTEDB-SN38 NPs was markedly higher than that of the small molecule CPT-11. The APTEDB-SN38 NPs delivered SN38 to tumor sites by both passive and active targeting. Finally, the APTEDB-SN38 NPs exhibited potent antitumor activities and low toxicities against EDB-expressing tumors (LLC, U87MG) in mice. This system merits further preclinical and clinical investigations for SN38 delivery.",

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AU - Lee, Yonghyun

AU - Kang, Sukmo

AU - Choi, Minsuk

AU - Lee, Soyoung

AU - Kim, Sunghyun

AU - Gujrati, Vipul

AU - Kim, Jinjoo

AU - Jon, Sangyong

PY - 2016/11/2

Y1 - 2016/11/2

N2 - Self-assembled nanoparticles (NPs) have been intensively utilized as cancer drug delivery carriers because hydrophobic anticancer drugs may be efficiently loaded into the particle cores. In this study, we synthesized and evaluated the therapeutic index of self-assembled NPs chemically conjugated to a fibronectin extra domain B-specific peptide (APTEDB) and an anticancer agent SN38. The APTEDB-SN38 formed self-assembled structures with a diameter of 58 ± 3 nm in an aqueous solution and displayed excellent drug loading, solubility, and stability properties. A pharmacokinetic study revealed that the blood circulation half-life of SN38 following injection of the APTEDB-SN38 NPs was markedly higher than that of the small molecule CPT-11. The APTEDB-SN38 NPs delivered SN38 to tumor sites by both passive and active targeting. Finally, the APTEDB-SN38 NPs exhibited potent antitumor activities and low toxicities against EDB-expressing tumors (LLC, U87MG) in mice. This system merits further preclinical and clinical investigations for SN38 delivery.

AB - Self-assembled nanoparticles (NPs) have been intensively utilized as cancer drug delivery carriers because hydrophobic anticancer drugs may be efficiently loaded into the particle cores. In this study, we synthesized and evaluated the therapeutic index of self-assembled NPs chemically conjugated to a fibronectin extra domain B-specific peptide (APTEDB) and an anticancer agent SN38. The APTEDB-SN38 formed self-assembled structures with a diameter of 58 ± 3 nm in an aqueous solution and displayed excellent drug loading, solubility, and stability properties. A pharmacokinetic study revealed that the blood circulation half-life of SN38 following injection of the APTEDB-SN38 NPs was markedly higher than that of the small molecule CPT-11. The APTEDB-SN38 NPs delivered SN38 to tumor sites by both passive and active targeting. Finally, the APTEDB-SN38 NPs exhibited potent antitumor activities and low toxicities against EDB-expressing tumors (LLC, U87MG) in mice. This system merits further preclinical and clinical investigations for SN38 delivery.

KW - SN38

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KW - cancer therapy

KW - extra domain B of fibronectin

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Self-assembled nanoparticles comprising aptide-SN38 conjugates for use in targeted cancer therapy

Abstract

Bibliographical note

Keywords

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