Cyclodextrin-Containing Polymers: Versatile Platforms of Drug Delivery Materials
Figure 9
RONDEL-based nanoparticles containing siRNA against EWS/Fli-1 were well tolerated by mice and efficacious in a disseminated murine model of Ewing’s sarcoma. (a) When administered twice weekly for four weeks, only nanoparticles containing AD-PEG-Tf and anti-EWS/Fli-1 siRNA (D) were effective in reducing tumor burden, as measured as integrated bioluminescence. Treatment group definitions: (A): vehicle control (D5W, 5 wt% dextrose in water), (B): anti-EWS-Fli1 siRNA without any other nanoparticle components (Naked siEFBP2), (C): nontargeting siRNA within Tf-targeted nanoparticles (Targ. form siCON#1), (D): anti-EWS-Fli1 siRNA within Tf-targeted nanoparticles (Targ. form siEFBP2), (E): anti-EWS-Fli1 siRNA within non-Tf-targeted nanoparticles (Nontarg. form siEFBP2). (b) When administered once to immunocompetent mice, these nanoparticles were well tolerated with respect to liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALKP), platelets (PLTs), indicators of kidney function (blood urea nitrogen (BUN) and creatinine (CRE)), and cytokine response (IL-12(p40) and IFN-α). Wild type denotes untreated mice; all other results are indicated by treatment group letter (A–E), as defined above, and the time point (2 or 24, in hours) at which blood was sampled (from [23]).
