The present invention provides compositions and methods for treatment of prostate cancer using siRNA cocktail sequences targeting multiple disease causing genes, and a combined regimen with both RNAi therapeutics and EEMP encapsulated magnetic nanoparticle therapeutics. The invention includes: 1) The algorithm for designing siRNA drug API (active pharmaceutical ingredient); 2)The compositions of multiple siRNA inhibiting expression of the multiple cancer causing genes; 3) The methods of designing siRNA duplexes with different lengths, different ends and to target the same genes from both human and mouse cells; 4) The methods of formulating various siRNA cocktail which are able to inhibit tumorigenic and angiogenesis; 5) The methods of using histidine-lysine copolymer (HKP), PAMAM dendrimer and Liposomal (DOTAP) carrier to enhance siRNA delivery into the cutaneous tissue; and 6) The methods of using two disease relevant mouse xenograft models to validate the siRNA cocktail for its efficacy on controlling tumor growth.
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