Engineering macrophage-derived exosomes for targeted chemotherapy of triple-negative breast cancer

Abstract

A macrophage exosome coated nanoplatform for targeted chemotherapy of triple-negative breast cancer.

Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

“…To resolve this issue, Mφ-EVs were engineered by removing their own contents and modifying addition of c-Met onto their surface, after which Dox-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were wrapped into the empty Mφ-EVs. These engineered EVs prolonged the release profile of Dox in vitro, and displayed high tumor targeting ability and excellent tumor inhibitory efficiency in mice with TNBC 133 . Another example is hybridizing EVs from M1-like macrophages with liposomes: the resulting hybrid Mφ-EVs exhibited higher cytotoxicity to multiple types of cancer cells, such as osteosarcoma and breast cancer cells, when loaded with Dox 134 .…”

“…at the days 1, 4, and 7 - Higher drug loading and targeting capacity towards cancer cells - Superior antineoplastic efficacy and prolonged lifespan 132 Breast cancer - RAW 264.7 cell line - Ultracentrifugation EVs (~110.8 nm) EVs loaded with DOX or PTX - Tumor volume reached ~50 mm 3 - EVs-PTX (0.5 mg/kg); EVs-DOX (2.5 mg/kg) by i.v. once every 3 days - Improved loading efficiency of DOX when pH close to PI, of PTX when dissolved in ethanol - Higher affinity towards tumor sites, more robust inhibitory potency on tumor growth and prolonged lifespan of both 133 - RAW 264.7 cell line - Ultracentrifugation Exos (~97.3 nm) EVs loaded with DOX - Tumor volumes reached 60 mm 3 - At DOX dose of 5 mg/kg by i.v. every 3 days for total 18 days - Prolonged circulation time of DOX and better accumulation of DOX at tumor tissue - Highest tumor inhibition efficacy - Decreased other tissue lesions 134 - J774A.1 cell line - Membrane filter extrusion EVs (~139 nm) Hybrid EVs with liposomes and loaded with DOX Unclear - Higher drug release in acidic microenvironment - Higher biocompatibility as a safe delivery system with lower cytotoxicity - Decreased K7M2, 4T1, and NIH/3T3 cell viability 135 Vaccine adjuvant Melanoma - RAW264.7 cell line with γ-IFN - Ultracentrifugation Exos (~50 nm) cytokines such as IL-6, IL-12, and γ-IFN - Tumor volume reached ~50 mm 3 - 10 μg EVs by single subcutaneously at 24 h after injection of vaccine - Elevated apoptosis of melanoma cancer cells - Decreased celluar scar tissues as well as many infiltrating immune cells - Significant inhibitory effects on tumor growth 131 …”

Exosomes: key players in cancer and potential therapeutic strategy

“…152 These engineered exosomes showed significantly improved cellular uptake efficiency and antitumor efficacy of doxorubicin. 153 Exosomes can also affect CSCs by targeting CSC-specific signaling pathways, such as Wnt, Notch, Hippo, Hedgehog, NF-κB, and TGF-β pathways. These pathways are of great significance for maintaining a series of biological functions, like self-renewal, differentiation, and tumorigenesis of CSCs.…”

Roles of Macrophages and Exosomes in Liver Diseases

“…Finally, several recent studies have reported on targeted drugs for exosomes. Exosomes can be used as carriers to deliver drugs to target areas, providing hope for the treatment of many diseases (63,64).…”