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Cationic liposome–DNA complexes (lipoplexes) are synthetic delivery systems that activate the innate immune system. They are composed of positively charged liposomes complexed with DNA. Upon cellular uptake via endocytosis, lipoplexes destabilize endosomal membranes, releasing DNA into the cytoplasm where it is sensed by intracellular pattern recognition receptors (PRRs) such as TLR9 and the cGAS-STING pathway, leading to a cytokine storm and activation of immune cells like NK cells, macrophages, and dendritic cells. This potent immunostimulatory activity makes lipoplexes valuable for cancer immunotherapy and vaccine adjuvant development. Their antitumor activity depends critically on NK cell activation.
Endocytic uptake, endosomal membrane destabilization, DNA release, activation of TLR9 and cytosolic DNA sensors (cGAS-STING pathway), cytokine storm induction.
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