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)

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5 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)14905-14913
Aantal pagina's9
TijdschriftACS Applied Materials and Interfaces
Volume12
Nummer van het tijdschrift13
DOI's
StatusGepubliceerd - 1 apr 2020

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