Carrier-free Arg-CpG augments antitumor efficacy by triggering specific immune activation.

Arg-CpG, a carrier-free poly(l-arginine)/CpG assembly, triggers macrophage reprogramming and robust antitumor immune responses in vivo, while selectively disrupting autophagy in 4T1 tumor cells.

• Why it matters: Nucleic acid cancer drugs often face low potency and rapid degradation, and conventional delivery vehicles can add toxicity. A carrier-free system that both delivers and activates immunity is needed.
• What they did: The authors built Arg-CpG by charge-driven assembly of poly(l-arginine) and unmethylated CpG, then assessed uptake, iNOS-linked nitric oxide generation, macrophage phenotype shifts, and autophagy effects in 4T1 and RAW264.7 cells.
• The result: Arg-CpG produces NO that synergizes with CpG to drive an antitumor macrophage phenotype and shows cell-type-dependent autophagy modulation, enabling selective tumor-cell killing without impairing normal immune cell viability or function.

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