నానోమెడిసిన్ & నానోటెక్నాలజీ జర్నల్

నైరూప్య

Size Effects of Nanocomplex on Tumor Associated Macrophages Targeted Delivery for Glioma

Lei Zou, Alejandro Macias sustaita, Tima Thomas, Lihn Do, Juan Rodriguez and Huanyu Dou

The size of functional nanocomplexes, which targets the brain tumor associated macrophages nanocomplex plays a very important role in their interaction with cells involving uptake, release and targeting selectivity. The size effects of nanocomplex on cell-based targeted delivery were studied to investigate if this phenomenon can be employed to combine the targeting peptide to provide a selective tumor associated macrophages targeted delivery system for anti-glioma therapy. Paclitaxel (PTX) was loaded into a core-shell structure of nanocomplex (PTX-Nanocomplex). Three different sizes of PTX-nanocomplex were prepared through nanoprecipitation. Rabies virus glycoprotein (RVG) peptide was conjugated to PTX-nanocomplex to form RVG-PTX-nanocomplex. Uptake, release, transportation and anti-glioma activities were studied in in vitro by using bone marrow derived macrophages (BMM) and tumor associated macrophages (TAMs), human glioma U87 cells, and neurons. The resulting RVG-PTX-nanocomplex had a spherical shape, with the size of 72 nm (small), 138 nm (medium), and 220 nm (large). The large-size RVG-PTX-nanocomplex showed greater uptake by BMM, but did not take by neurons. Co-cultivation of U87 and TAMs pre-loaded with largesize RVG-PTX-nanocomplexes provided significant anti-glioma activities. More importantly, large-size RVG-PTXnanocomplexes were selectively targeted to TAMs and effectively transported to U87 cells with lower side effects. We concluded that the large-size RVG-PTX-nanocomplex had promising potential uses in the TAMs targeted delivery system for glioma therapy.