Research Projects

Tumor-associated macrophages (TAMs) make up 50% of solid tumor mass and are a primary target for immunotherapeutic approaches due to their role in tumor growth, angiogenesis, metastasis, and cancer stem cell development. Toll-like receptors and antibodies targeting TAMs can cause systemic inflammation and interfere with chemotherapy. Arginase-I (Arg-1) is a critical marker of M2-type TAMs that converts L-arginine to polyamines required by rapidly dividing cancer cells. The transcription factor Fos-related antigen-1 (Fra-1) has been shown to negatively regulate Arg-1 expression. This study proposes developing a cationic mannosylated chitosan polysaccharide-based nanocarrier for Fra-1 gene delivery to TAMs and evaluating its anti-metastatic potential. The nanocarriers will be characterized by zeta potential, particle size, mobility shift assay, polysaccharide-DNA association assay, DNase-I protection and release assay. The anti-metastatic potential of nanocarriers will be evaluated through western blotting on nanoparticle-mediated delivery and cell invasion assays. A syngenic breast tumor model will be developed using luciferase-expressing cells 4T1-12b in T4 mammary fat pad of female BALB/c mice. The study will also investigate the effect of nanocarriers on tumor spread to distant organs via bioluminescence imaging and hematoxylin and Eosin staining. This study is the first to formulate a cationic mannosylated polysaccharide-based carrier system for Fra-1 gene delivery to specifically TAMs, potentially serving as successful adjuvant immunotherapy and anti-neoplastic agents for breast cancer treatment.