Paclitaxel-Loaded Expansile Nanoparticles Delay Local Recurrence in a Heterotopic Murine Non-Small Cell Lung Cancer Model

Abstract

Surgical resection remains the most effective treatment option for patients with early stage non-small cell lung cancer; however, comorbidities and poor pulmonary reserve often limit the extent of resection. Limited resections are associated with a twofold to threefold increase in locoregional recurrence, suggesting that microscopic disease remains near the resection margin. We hypothesized that local delivery of paclitaxel through 100-nm expansile polymer nanoparticles (pax-eNP) immediately after tumor resection could prevent local recurrence. Primary tumors, initiated on the dorsum of C57BL/6J mice through subcutaneous injection of 750,000 Lewis lung carcinoma cells, were excised when tumor volume reached 300 mm(3). After resection, animals were randomized to receive 300 μg paclitaxel intravenously or as pax-eNP locally at the tumor resection site versus unloaded eNP or saline controls. In all mice receiving saline, unloaded eNP, or paclitaxel intravenously, visible local tumor recurrence developed at a median of 6 days. In contrast, tumor recurrence after pax-eNP was delayed to 10 days (pax-eNP versus all other groups, Kaplan-Meier, p < 0.05). Delay in local recurrence was associated with increased survival in the pax-eNP group (16 days) versus all other groups (11 and 12 days, p < 0.05). The pax-eNP placed at the time of surgical resection delayed local tumor recurrence and modestly prolonged survival in a murine Lewis lung carcinoma recurrence model.