B cell–specific delivery of the payload and lack of immunostimulation by RIT-INP in whole blood from CLL patients. (A) Nonselectivity of free FAM-ODN (1μM) in PBMCs. (B) Selectivity of RIT-INP–encapsulated FAM-ODN (1μM) in PBMCs. (C) Fold changes of costimulatory molecules (CD40 and CD86) in whole blood from CLL patients. Expression was determined by flow cytometry. Data were normalized to PBS-treated blood. (D) Cytokine production of IL-6 (n = 4) and TNF-α (n = 4) in serum from patient whole blood treated with PBS, free G3139 (25 μg/mL), and RIT-INP–G3139 (25 μg/mL) or HER-INP–G3139 (25 μg/mL). Cytokine release was determined by ELISA.