Polycationic carbosilane dendrimer decreases angiogenesis and tumor-associated macrophages in tumor-bearing mice

Abstract

Therapies against cancer have been improved and progressed during recent decades, initially were using chemotherapeutic drugs, which directly affect tumor cells, but nowadays are focused in cellular therapies aimed at treating the tumor stroma, because tumor and stromal cells jointly control development and tumor progression. Immunotherapy is of great relevance because it could modify the tumor stroma, controlling tumor growth. Tumor-associated macrophages have been proposed as target cells owing to the positive correlation between the high content of macrophages and the adverse prognosis of tumor development. 2G-03NN24 dendrimer had previously shown immunomodulatory effects by reducing the functional capabilities of human anti-inflammatory macrophages, leading them to a pro-inflammatory state, and thereby helping to control tumor development. New dendrimer capabilities against tumor mass are described and presented in in vivo studies using tumor-bearing mice. MC38 cells were used to induce tumors in C57BL/6 mice. Tumor growth was evaluated during 21 days and tumors were stained with hematoxylin/eosin to analyze the histopathology features. Tumor histopathology studies show that 2G-03NN24 dendrimer decreases the tumor size and the number of intratumoral blood vessels. Furthermore, cellular populations on tumor mass were analyzed by an immunofluorescence assay. Evaluation of tumor-associated macrophages indicates that 2G-03NN24 dendrimer reduces the amount of tumor-associated macrophages, creating a more favorable microenvironment within tumors. Data defines 2G-03NN24 as a candidate for finding a new antitumor compound based on cellular therapies.