Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine

The compound 7-ethyl-10-hydroxy-camptothecin (SN38) is a broad-spectrum antitumor agent whose applications are greatly limited by its poor solubility. Therefore, irinotecan, the hydrophilic derived prodrug of SN38, has been developed as the commercial formulation Campto ® for colorectal cancer. How...

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Main Authors: Guanting Li, Qianhui Jin, Fengli Xia, Shuwen Fu, Xuanbo Zhang, Hongying Xiao, Chutong Tian, Qingzhi Lv, Jin Sun, Zhonggui He, Bingjun Sun
Format: Article
Language:English
Published: Compuscript Ltd 2023-01-01
Series:Acta Materia Medica
Online Access:https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0003
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author Guanting Li
Qianhui Jin
Fengli Xia
Shuwen Fu
Xuanbo Zhang
Hongying Xiao
Chutong Tian
Qingzhi Lv
Jin Sun
Zhonggui He
Bingjun Sun
author_facet Guanting Li
Qianhui Jin
Fengli Xia
Shuwen Fu
Xuanbo Zhang
Hongying Xiao
Chutong Tian
Qingzhi Lv
Jin Sun
Zhonggui He
Bingjun Sun
author_sort Guanting Li
collection DOAJ
description The compound 7-ethyl-10-hydroxy-camptothecin (SN38) is a broad-spectrum antitumor agent whose applications are greatly limited by its poor solubility. Therefore, irinotecan, the hydrophilic derived prodrug of SN38, has been developed as the commercial formulation Campto ® for colorectal cancer. However, only 1% to 0.1% of irinotecan is converted to active SN38 in vivo, thus leading to unsatisfactory antitumor activity in clinical settings. Herein, we report a smart stimuli-responsive SN38 prodrug nanoassembly for efficient cancer therapy. First, SN38 was conjugated with an endogenous lipid, cholesterol (CST), via a redox dual-responsive disulfide bond (namely SN38-SS-CST). The prodrug self-assembled into uniform prodrug nanoassemblies with good colloidal stability and ultrahigh drug loading. SN38-SS-CST NPs released sufficient SN38 in the redox environments of tumor cells but remained intact in normal tissues. Finally, SN38-SS-CST NPs potently inhibited the growth of colon cancer without causing systemic toxicity, thus indicating their promise as a translational chemotherapeutic nanomedicine.
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spelling doaj-art-ae6512a5df90477c8a75cb397dae81d12025-08-20T02:34:56ZengCompuscript LtdActa Materia Medica2737-79462023-01-0121546310.15212/AMM-2023-0003Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicineGuanting LiQianhui JinFengli XiaShuwen FuXuanbo ZhangHongying XiaoChutong TianQingzhi LvJin SunZhonggui HeBingjun SunThe compound 7-ethyl-10-hydroxy-camptothecin (SN38) is a broad-spectrum antitumor agent whose applications are greatly limited by its poor solubility. Therefore, irinotecan, the hydrophilic derived prodrug of SN38, has been developed as the commercial formulation Campto ® for colorectal cancer. However, only 1% to 0.1% of irinotecan is converted to active SN38 in vivo, thus leading to unsatisfactory antitumor activity in clinical settings. Herein, we report a smart stimuli-responsive SN38 prodrug nanoassembly for efficient cancer therapy. First, SN38 was conjugated with an endogenous lipid, cholesterol (CST), via a redox dual-responsive disulfide bond (namely SN38-SS-CST). The prodrug self-assembled into uniform prodrug nanoassemblies with good colloidal stability and ultrahigh drug loading. SN38-SS-CST NPs released sufficient SN38 in the redox environments of tumor cells but remained intact in normal tissues. Finally, SN38-SS-CST NPs potently inhibited the growth of colon cancer without causing systemic toxicity, thus indicating their promise as a translational chemotherapeutic nanomedicine.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0003
spellingShingle Guanting Li
Qianhui Jin
Fengli Xia
Shuwen Fu
Xuanbo Zhang
Hongying Xiao
Chutong Tian
Qingzhi Lv
Jin Sun
Zhonggui He
Bingjun Sun
Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine
Acta Materia Medica
title Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine
title_full Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine
title_fullStr Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine
title_full_unstemmed Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine
title_short Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine
title_sort smart stimuli responsive carrier free nanoassembly of sn38 prodrug as efficient chemotherapeutic nanomedicine
url https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0003
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