Nanoparticle-Loaded Polarized-Macrophages for Enhanced Tumor Targeting and Cell-Chemotherapy

Abstract

Cell therapy is a promising strategy for cancer therapy. However, its therapeutic efficiency remains limited due to the complex and immunosuppressive nature of tumor microenvironments. In this study, the “cell-chemotherapy” strategy was presented to enhance antitumor efficacy. M1-type macrophages, which are therapeutic immune cells with both of immunotherapeutic ability and targeting ability, carried sorafenib (SF)-loaded lipid nanoparticles (M1/SLNPs) were developed. M1-type macrophages were used both as therapeutic tool to provide immunotherapy and as delivery vessel to target deliver SF to tumor tissues for chemotherapy simultaneously. M1-type macrophages were obtained by polarizing macrophages using lipopolysaccharide, and M1/SLNPs were obtained by incubating M1-type macrophages with SLNP. Tumor accumulation of M1/SLNP was increased compared with SLNP (p < 0.01), which proved M1/SLNP could enhance tumor targeting of SF. An increased ratio of M1-type macrophages to M2-type macrophages, and the CD3+CD4+ T cells and CD3+CD8+ T cell quantities in tumor tissues after treatment with M1/SLNP indicated M1/SLNP could relieve the immunosuppressive tumor microenvironments. The tumor volumes in the M1/SLNP group were significantly smaller than those in the SLNP group (p < 0.01), indicating M1/SLNP exhibited enhanced antitumor efficacy. Consequently, M1/SLNP showed great potential as a novel cell-chemotherapeutic strategy combining both cell therapy and targeting chemotherapy.

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

“…Combinatorial treatment strategies targeting these two pathways in a synergistic manner are expected to have a greater impact on the inhibition of tumor growth, than PD1/PDL1 checkpoint inhibitors or anti- SEMA4D monotherapies. The combination of TAM-targeted drugs with chemotherapy could also improve the therapeutic effect of chemotherapeutic drugs, which when administered alone can increase the infiltration of TAMs into tumor tissues [ 258 , 296 ]. Furthermore, the combination of M2- TAM-targeting by Au@SiO2 (GNPs) NPs conjugated with a CD163 antibody with radiation has resulted in more effective tumor growth delay than radiation alone [ 259 ].…”

ARV-825 Demonstrates Antitumor Activity in Gastric Cancer via MYC-Targets and G2M-Checkpoint Signaling Pathways

“…Therefore, a deep insight on the related mechanism of gastric cancer and the search for markers or therapeutic targets with high sensitivity and specificity are useful to improve the quality of life and increase the survival rate of patients with gastric cancer. In order to solve various problems in cancer treatment, many studies also provided direction for our treatment of gastric cancer, such as polarized macrophages, for enhancing tumor targeting and drug sensitivity ( 5 , 6 ), induced pluripotent stem cells (iPS) enhancing immunotherapy against cancer ( 7 ), and review in tumor microenvironment ( 8 ).…”

Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

“…One source is primary macrophages, such as bone marrow-derived macrophages, alveolar macrophages, and peritoneal macrophages. The second source is cell lines, including the mouse macrophage cell lines RAW264.7 and J774A.1 and the human peripheral blood monocyte cell line THP-1 (24,41,(88)(89)(90)(91). NPL-Ms can carry a variety of NPs, including liposomes (92,93), magnetic NPs (94,95), polymeric NPs (96,97), gold (AU) NPs (98)(99)(100)(101), and others (102,103).…”

“…Many studies have demonstrated that NP-loaded macrophages (NPL-Ms) can directionally migrate to tumors and transport the payload to tumor cells, leading to a pronounced antitumor effect (39,40). Moreover, after reaching tumors, these engineered macrophages can exert additional effects by stimulating anticancer immune responses (24,41). In this review, we first introduce the origin, differentiation, and function of macrophages as well as the application of nanotechnology in anticancer therapy.…”

“…Nanoparticles (NPs) are synthetic structures with a nanoscale dimension and can be generally divided into two categories: organic NPs (i.e., liposomes, polymer micelles) and inorganic NPs (i.e., gold, silver, iron oxide) ( 23 ). NPs have been used to deliver a variety of anticancer agents, such as traditional chemotherapeutic drugs ( 23 ), targeted drugs ( 24 ), and genetic materials [i.e., messenger RNA ( 25 ), small interfering RNA ( 26 ), and the CRISPR/Cas9 genetic editing system ( 27 )]. Due to their distinctive physicochemical properties, NPs can enhance the delivery of anticancer agents to tumors by both passive and active mechanisms ( 21 , 28 ).…”