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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 α 3 β 1 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. α 3 β 1 integrin-targeting polymersomal docetaxel emerges as an advanced nanotherapeutic for NSCLC treatment.

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

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