Multifunctional biomimetic liposomal nucleic acid scavengers inhibit the growth and metastasis of breast cancer†

Abstract

Chemotherapy and surgery, though effective in cancer treatment, trigger the release of nucleic acid-containing pro-inflammatory compounds from damaged tumor cells, known as nucleic acid-associated damage-associated molecular patterns (NA-DAMPs). This inflammation promotes tumor metastasis, and currently, no effective treatment exists for this treatment-induced inflammation and subsequent tumor metastasis. To address this challenge, we developed a biomimetic liposome complex (Lipo-Rh₂) incorporating a hybrid structure of liposomes and dendritic polymers, mimicking cell membrane morphology. Lipo-Rh₂ leverages the multivalent surface properties of dendritic polymers to clear cell-free nucleic acids while serving as both a structural stabilizer and targeting ligand via embedded ginsenoside Rh₂. Experimental data show that Lipo-Rh₂ effectively reduces free nucleic acids in mouse serum through charge interactions, downregulates Toll-like receptor expression, decreases inflammatory cytokine secretion, and inhibits both primary tumor growth and metastasis. Compared to the current nucleic acid scavenger PAMAM-G3, Lipo-Rh₂ demonstrates stronger antitumor effects, lower toxicity, and enhanced targeting capabilities. This biomimetic liposome-based nucleic acid scavenger represents a novel approach to nucleic acid clearance, expanding the framework for designing effective therapeutic agents.