α3β1 Integrin-Targeting Polymersomal Docetaxel as an Advanced Nanotherapeutic for Nonsmall Cell Lung Cancer Treatment.
Yan ZouYinping SunBeibei GuoYaohua WeiYifeng XiaZhenyuan HuangfuFenghua MengJan C M Van HestJiandong YuanZhiyuan ZhongPublished in: ACS applied materials & interfaces (2020)
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.
Keyphrases
- small cell lung cancer
- cancer therapy
- drug delivery
- advanced non small cell lung cancer
- locally advanced
- squamous cell carcinoma
- end stage renal disease
- randomized controlled trial
- chronic kidney disease
- photodynamic therapy
- mesenchymal stem cells
- clinical trial
- adipose tissue
- cell therapy
- metabolic syndrome
- prognostic factors
- cell migration
- brain metastases
- replacement therapy
- patient reported
- solid phase extraction