Tumor-infiltrating macrophages (TIMs) are a type of immune cell that can be found in and around solid tumors. Macrophages are highly specialized immune system cells that aid the body in identifying and combating harmful invaders.
To defend the body from potentially fatal diseases like cancer, M1-like macrophages in particular identify and eliminate tumor cells as well as release protective chemokines like interleukin (IL)-6 and tumor-necrosis factor α (TNF α).
However, not all macrophages show anti-tumor potential. M2-like macrophages are one particular type of macrophage that encourages tumor growth. Fortunately, by altering the physiological milieu of the cells, the appropriate macrophage phenotype a collection of characteristics originating from the genetic composition of the macrophage can be triggered.
Interestingly, multiple nanomaterial-based immunomodulators have been developed in the past, which are known to facilitate the phenotype transition of macrophages from M0 to M1.
TIMs can have both positive and negative effects on tumor growth and progression. On one hand, they can help to stimulate the immune system to attack the tumor and promote the destruction of cancer cells.
On the other hand, they can also promote the growth and spread of cancer cells by providing them with the nutrients they need to survive and by suppressing the immune system’s ability to attack them.
Unlike metal or synthetic polymer-based nanoparticles, these BMPPs exhibit excellent biocompatibility, high efficacy, and precise tunability in immunomodulatory effectiveness. With such encouraging findings, we are motivated to continue our research into cancer immunotherapy applications.
Dr. Yuan Yao
Recently, a team of researchers led by Dr. Na Kong and Dr. Yuan Yao from the ShanghaiTech University, China, conducted a study to design novel immunomodulators biomimetic polypeptides (BMPPs) that could activate tumor-infiltrating macrophages, i.e., M1-like macrophages. Their study was published in BioDesign Research.
Elaborating on the development of BMPPs, Dr. Yao remarks, “Combining de novo protein design and biosynthesis techniques, we designed a BMPP self-assembled nano-immunomodulator to trigger the activation of a specific macrophage phenotype. It was intended to be made up of (GGSGGPGGGPASAAANSASRATSNSP)n, the RGD motif from collagen, and the IKVAV motif from laminin.”
It’s crucial to remember that previously created nano-immunomodulators showed clear drawbacks such biotoxicity and poor biocompatibility.
To overcome such limitations, Dr. Yao and team tried a unique approach. They created and biosynthesized a biomimetic nanofibril, a highly structured, stable structure made up of repeated, self-assembling building components.
They did this by validating the anticipated monomers and higher-order complexes using molecular dynamics simulations, which are computational studies that simulate the motion of big biomolecules like polypeptides and proteins as well as atoms, molecules, and even whole molecules.
Although previous research has demonstrated that the RGD and IKVAV motifs include amino acid residues with putative immunomodulatory properties, the resulting BMPPs specifically housed these motifs.
Following biosynthesis, the team conducted a variety of assays including enzyme-linked immunosorbent assay (ELISA), to test the efficacy of the newly biosynthesized BMPPs. Cell proliferation assays conducted using RAW264.7 cells demonstrated the general biosafety and cytocompatibility of BMPPs.
Moreover, results from ELISA revealed that BMPP nano-immunomodulators increased the protein expression levels of IL-6 and TNFα, without affecting the expression levels of IL-10.
Because of this, it was evident that M1 macrophage polarization happened at high BMPP concentrations and that BMPP nano-immunomodulators were probably what were activating the M1-like macrophages.
“Unlike metal or synthetic polymer-based nanoparticles, these BMPPs exhibit excellent biocompatibility, high efficacy, and precise tunability in immunomodulatory effectiveness. With such encouraging findings, we are motivated to continue our research into cancer immunotherapy applications,” says Dr. Yao.
