PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors
Nanoparticle uptake can be enhanced by ultrasonication in the presence of microbubbles in skeletal muscle in vivo. (a) Gracilis skeletal muscle cross-sections illustrating fluorescent polystyrene nanoparticle (NP) delivery for each treatment. (A)–(I) Muscle treated with ultrasound (US) + microbubbles (MB) + nanoparticles (NP) combinations. For the conditions of US + MB + NP, NPs (red) accumulate in vessel walls and muscle interstitium (BS-1 lectin staining, green). For muscle treated with US + NP, NPs colocalized with endothelium but minimal interstitial deposition was observed. Muscle treated with MB + NP was almost void of NP. (J) Bar graph representing the fraction of interstitial area (regions outside of muscle fibers and vascular structures) or endothelial cell area (cells comprising the walls of blood vessels) occupied by NP. Values are means with standard deviations. *indicates significantly different (P < 0.05) than interstitial area of all other groups. +indicates significantly different (P < 0.05) than endothelial cell area of all other groups. (b) The delivery of FGF-2 bearing nanoparticles by ultrasonic microbubble destruction elicits arteriogenic remodeling in gracilis adductor muscle. (A)–(D) Representative whole-mount images of fluorescently labeled SM α-actin+ vessels in gracilis adductor muscles 7 and 14 days after FGF-2 (A) and (B) and BSA (C) and (D) treatment. Note the significant increase in arteriolar caliber and density in FGF-2-treated muscles. (E) Bar graph of arteriole line intersections at both time points for FGF-2, BSA, and sham surgery treatment. Values are means with standard errors. *indicates significantly different (P < 0.05) than BSA and sham surgery at day 14. Reprinted from  with permission from Wiley.