Anionic Polyphosphazene Nanoparticles Enable Targeted Docetaxel Delivery in Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) remains a major clinical challenge due to its poor prognosis and limited therapeutic options. Although docetaxel (DTX) is a frontline chemotherapeutic for NSCLC, its clinical use is constrained by low aqueous solubility and dose-limiting systemic toxicity. To overcome these barriers, we developed a polyphosphazene–docetaxel conjugate (Polytaxel, PTX) with favorable NOAEL characteristics. Here, we demonstrate that PTX exhibits significantly enhanced anti-tumor activity against NSCLC in vitro and in vivo, with minimal adverse effects in A549 xenograft model. Detailed in vivo metabolic analysis reveals a well-defined biodegradation and clearance pathway, underscoring its translational potential. These findings position PTX as a promising nanomedicine platform for safe and effective NSCLC chemotherapy.