α3β1 Integrin-Targeting Polymersomal Docetaxel as an Advanced Nanotherapeutic for Nonsmall Cell Lung Cancer Treatment

Yan Zou; Yinping Sun; Beibei Guo; Yaohua Wei; Yifeng Xia; Zhenyuan Huangfu; Fenghua Meng; Jan C.M. van Hest; Jiandong Yuan; Zhiyuan Zhong

doi:10.1021/acsami.0c01069

α₃β₁ Integrin-Targeting Polymersomal Docetaxel as an Advanced Nanotherapeutic for Nonsmall Cell Lung Cancer Treatment

Yan Zou, Yinping Sun, Beibei Guo, Yaohua Wei, Yifeng Xia, Zhenyuan Huangfu, Fenghua Meng (Corresponding author), Jan C.M. van Hest, Jiandong Yuan, Zhiyuan Zhong (Corresponding author)

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

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Abstract

Docetaxel (DTX) widely used for treating nonsmall cell lung cancer (NSCLC) patients is associated with dose-limiting side effects, especially neurotoxicity and myelosuppression. Here, we have developed cyclic cNGQGEQc peptide-directed polymersomal docetaxel (cNGQ-PS-DTX) as a targeted and multifunctional formulation for NSCLC. cNGQ-PS-DTX carrying 8.1 wt % DTX had a size of 93 nm, neutral surface charge, high stability, and glutathione-triggered DTX release behavior. Cytotoxicity studies demonstrated a clearly better antitumor activity of cNGQ-PS-DTX in α₃β₁ integrin overexpressing A549 human lung cancer cells than free DTX and nontargeted PS-DTX. cNGQ-PS-DTX showed a remarkably high tolerability (over 8 times better than free DTX) and slow elimination in mice. Importantly, cNGQ-PS-DTX exhibited greatly improved tumor accumulation and higher suppression of subcutaneous and orthotopic A549 xenografts as compared to PS-DTX and free DTX controls. α₃β₁ integrin-targeting polymersomal docetaxel emerges as an advanced nanotherapeutic for NSCLC treatment.

Original language	English
Pages (from-to)	14905-14913
Number of pages	9
Journal	ACS Applied Materials and Interfaces
Volume	12
Issue number	13
DOIs	https://doi.org/10.1021/acsami.0c01069
Publication status	Published - 1 Apr 2020

Keywords

chemotherapy
docetaxel
lung cancer
polymersomes
targeted delivery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/acsami.0c01069

acsami.0c01069Final published version, 7.11 MBLicence: TAVERNE

Cite this

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title = "α3β1 Integrin-Targeting Polymersomal Docetaxel as an Advanced Nanotherapeutic for Nonsmall Cell Lung Cancer Treatment",

abstract = "Docetaxel (DTX) widely used for treating nonsmall cell lung cancer (NSCLC) patients is associated with dose-limiting side effects, especially neurotoxicity and myelosuppression. Here, we have developed cyclic cNGQGEQc peptide-directed polymersomal docetaxel (cNGQ-PS-DTX) as a targeted and multifunctional formulation for NSCLC. cNGQ-PS-DTX carrying 8.1 wt % DTX had a size of 93 nm, neutral surface charge, high stability, and glutathione-triggered DTX release behavior. Cytotoxicity studies demonstrated a clearly better antitumor activity of cNGQ-PS-DTX in α3β1 integrin overexpressing A549 human lung cancer cells than free DTX and nontargeted PS-DTX. cNGQ-PS-DTX showed a remarkably high tolerability (over 8 times better than free DTX) and slow elimination in mice. Importantly, cNGQ-PS-DTX exhibited greatly improved tumor accumulation and higher suppression of subcutaneous and orthotopic A549 xenografts as compared to PS-DTX and free DTX controls. α3β1 integrin-targeting polymersomal docetaxel emerges as an advanced nanotherapeutic for NSCLC treatment.",

keywords = "chemotherapy, docetaxel, lung cancer, polymersomes, targeted delivery",

author = "Yan Zou and Yinping Sun and Beibei Guo and Yaohua Wei and Yifeng Xia and Zhenyuan Huangfu and Fenghua Meng and {van Hest}, {Jan C.M.} and Jiandong Yuan and Zhiyuan Zhong",

year = "2020",

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doi = "10.1021/acsami.0c01069",

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TY - JOUR

T1 - α3β1 Integrin-Targeting Polymersomal Docetaxel as an Advanced Nanotherapeutic for Nonsmall Cell Lung Cancer Treatment

AU - Zou, Yan

AU - Sun, Yinping

AU - Guo, Beibei

AU - Wei, Yaohua

AU - Xia, Yifeng

AU - Huangfu, Zhenyuan

AU - Meng, Fenghua

AU - van Hest, Jan C.M.

AU - Yuan, Jiandong

AU - Zhong, Zhiyuan

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Docetaxel (DTX) widely used for treating nonsmall cell lung cancer (NSCLC) patients is associated with dose-limiting side effects, especially neurotoxicity and myelosuppression. Here, we have developed cyclic cNGQGEQc peptide-directed polymersomal docetaxel (cNGQ-PS-DTX) as a targeted and multifunctional formulation for NSCLC. cNGQ-PS-DTX carrying 8.1 wt % DTX had a size of 93 nm, neutral surface charge, high stability, and glutathione-triggered DTX release behavior. Cytotoxicity studies demonstrated a clearly better antitumor activity of cNGQ-PS-DTX in α3β1 integrin overexpressing A549 human lung cancer cells than free DTX and nontargeted PS-DTX. cNGQ-PS-DTX showed a remarkably high tolerability (over 8 times better than free DTX) and slow elimination in mice. Importantly, cNGQ-PS-DTX exhibited greatly improved tumor accumulation and higher suppression of subcutaneous and orthotopic A549 xenografts as compared to PS-DTX and free DTX controls. α3β1 integrin-targeting polymersomal docetaxel emerges as an advanced nanotherapeutic for NSCLC treatment.

AB - Docetaxel (DTX) widely used for treating nonsmall cell lung cancer (NSCLC) patients is associated with dose-limiting side effects, especially neurotoxicity and myelosuppression. Here, we have developed cyclic cNGQGEQc peptide-directed polymersomal docetaxel (cNGQ-PS-DTX) as a targeted and multifunctional formulation for NSCLC. cNGQ-PS-DTX carrying 8.1 wt % DTX had a size of 93 nm, neutral surface charge, high stability, and glutathione-triggered DTX release behavior. Cytotoxicity studies demonstrated a clearly better antitumor activity of cNGQ-PS-DTX in α3β1 integrin overexpressing A549 human lung cancer cells than free DTX and nontargeted PS-DTX. cNGQ-PS-DTX showed a remarkably high tolerability (over 8 times better than free DTX) and slow elimination in mice. Importantly, cNGQ-PS-DTX exhibited greatly improved tumor accumulation and higher suppression of subcutaneous and orthotopic A549 xenografts as compared to PS-DTX and free DTX controls. α3β1 integrin-targeting polymersomal docetaxel emerges as an advanced nanotherapeutic for NSCLC treatment.

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