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Uveal melanoma (UM) is rare yet the most common and malignant primary intraocular tumor in adults. Due to the lack of effective treatment, the mortality rate of UM has remained high over the past few decades. In the present study, hyaluronic acid (HA) coated chitosan (Chi)/siRNA ternary complexes have been developed and characterized as a novel therapeutic strategy molecularly targeting hypoxia-inducible factor 1α (HIF-1α) pathway for the treatment of UM. The cytotoxicity, cellular uptake, and siRNA silencing effect of the developed siRNA complexes were evaluated. In addition, whether the developed ternary complexes can inhibit UM migration and invasion was investigated. Results showed that the developed ternary siRNA complexes were negatively charged and with a particle size below 190 nm. The ternary siRNA complexes showed excellent cellular uptake and lysosome escape ability with low …