Sialic acid-modified nanomedicines modulate neutrophils for dual therapy of cancer and sepsis: addressing neglected sepsis comorbidities during cancer treatment.

Summary

An SA-modified paclitaxel liposome that binds L-selectin on neutrophils selectively depleted hyperactive neutrophils, reduced tissue infiltration, and improved survival in murine melanoma and sepsis models. In a late-stage cancer plus sepsis model, 72-hour survival was 66.7% with PTX-SAL versus 0% with conventional paclitaxel solution, suggesting targeted nanomedicine can mitigate treatment-related immune toxicity while controlling inflammation.

Key Findings

• PTX-SAL bound L-selectin on neutrophils, selectively eliminating hyperactive neutrophils and blocking their migration.
• In sepsis and melanoma mouse models, PTX-SAL showed superior efficacy and safety versus paclitaxel solution.
• In a late-stage tumor plus sepsis model, 72-hour survival was 66.7% with PTX-SAL, whereas all animals died within 24 hours with paclitaxel solution.

Clinical Implications

For oncology patients at high risk for sepsis, neutrophil-targeted nanomedicines could offer anti-tumor efficacy while reducing sepsis-related mortality by avoiding nonspecific immune cytotoxicity. These findings justify translational studies to evaluate safety, dosing, and synergy with antimicrobials and source control.

Limitations

• Preclinical animal data; human pharmacokinetics, immunologic effects, and safety remain unknown.
• Comparisons to standard sepsis care (e.g., antibiotics, fluids, vasopressors) were not detailed.

Future Directions

Conduct dose-ranging and safety studies in large animals, explore combination with antimicrobials and source control, and assess immunologic balance (host defense vs. hyperinflammation) in translational trials.