Cancer immune therapy using engineered ‛tail-flipping' nanoliposomes targeting alternatively activated macrophages.

Alternatively-activated, M2-like tumor-associated macrophages (TAM) strongly contribute to tumor growth, invasiveness and metastasis. Technologies to disable the pro-tumorigenic function of these TAMs are of high interest to immunotherapy research. Here we show that by designing engineered nanoliposomes bio-mimicking peroxidated phospholipids that are recognised and internalised by scavenger receptors, TAMs can be targeted.

Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer.

Tumor-associated macrophages (TAMs) are the key effector cells in the tumor microenvironment and induce neoangiogenesis, matrix remodeling, and metastasis while suppressing the tumor immune system. These protumoral macrophages display an M2 phenotype induced by IL-4 and IL-13 cytokines. In this study, we hypothesized that the inhibition of the signal transducer and activator of transcription 6 (Stat6) pathway, a common downstream signaling pathway of IL-4 and IL-13, may be an interesting strategy by which to inhibit TAM differentiation and, thus, their protumorigenic activities.

Nanomedicine Strategies to Target Tumor-Associated Macrophages.

In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors.

Differential uptake of nanoparticles by human M1 and M2 polarized macrophages: protein corona as a critical determinant.

Aim: To investigate the interaction behavior of M1- and M2-type macrophages with nanoparticles of different sizes with/without the presence of serum.

Materials & Methods: THP-1 human monocytes were differentiated into M1 and M2 macrophages, and the uptake of silica nanoparticle (50-1000 nm) was studied using flow cytometry and different microscopies.

Results: Without serum, higher uptake of all-sized nanoparticles was observed by M1 compared with M2.