Utilizing small interfering RNAs (siRNAs) to silence disease-associated genes holds promise as a potential therapeutic strategy. However, the greatest challenge for RNAi remains the delivery of siRNA to target tissues or cells. Specifically lymphocytes are difficult to transduce by conventional methods but represent good targets for anti-inflammatory therapeutics. Integrins are an important class of cell adhesion receptors on leukocytes. Antibodies to integrins have been used to inhibit inflammatory reactions in patients. Here, we describe a strategy to deliver the siRNA cargo to leukocytes by stabilized nanoparticles surface-decorated with antibodies to integrin as targeting moieties. A detailed methodology for preparation of the integrin-targeted stabilized nanoparticles (I-tsNPs) and their delivery in vitro and in vivo is discussed.