Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 13, Pages 14905-14913Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c01069
Keywords
lung cancer; polymersomes; docetaxel; chemotherapy; targeted delivery
Funding
- National Natural Science Foundation of China [NSFC 51773146, 51861145310, 51561135010, 51633005, 51761135117]
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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. cNGQPS-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 alpha(3)beta(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, cNGQPS-DTX exhibited greatly improved tumor accumulation and higher suppression of subcutaneous and orthotopic A549 xenografts as compared to PS-DTX and free DTX controls. alpha(3)beta(1) integrin-targeting polymersomal docctawl emerges as an advanced nanotherapeutic for NSCLC treatment.
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