Lipoxin A4 (LXA₄) versus Nanolipoxin A4 (Nano-LXA₄) for osteosarcoma

Lipoxin A4 (LXA₄) is a specialized pro-resolving lipid mediator with reported antitumor and immunomodulatory activity, but its translation is limited by chemical lability and formulation constraints. Here, we evaluated free LXA₄ ("Lipoxin") versus a Pluronic F-127 micellar nanoformulation ("Nanolipoxin") in a human osteosarcoma patient-derived xenograft (PDX) model and assessed In vivo biodistribution using ^99mTc labeling. Nanolipoxin exhibited nanostructures with heterogeneous dimensions by SEM (mean length 65 nm; mean diameter 41 nm) and was stored at 2-8 °C to preserve stability. PDX-bearing NSG mice received intraperitoneal treatment (1 µg; n = 3/group) and were monitored for 15 days. Both Lipoxin and Nanolipoxin produced a modest inhibition of tumor growth versus saline, reaching statistical significance on day 9 (*P = 0.0319) and day 15 (**P = 0.0076), while no significant differences were detected between the two active treatments. No clinical toxicity was observed (clinical score 0; stable body weight). Serum biochemistry showed no ALT differences versus control and an AST decrease for both treatments; Nanolipoxin increased lipase relative to control (*P = 0.0334). Dynamic planar scintigraphy demonstrated preferential tumor retention of ^99mTc-Nanolipoxin at 60 min (lesion 350.47 kBq), with moderate renal/hepatic uptake and low bladder signal. Collectively, these data support LXA₄-based strategies in osteosarcoma and demonstrate that nanoformulation provides tumor-localizing behavior while maintaining an acceptable short-term tolerability profile in this PDX setting.