Nanotherapy delivery of c-myc inhibitor targets Protumor Macrophages and preserves Antitumor Macrophages in Breast Cancer.

Theranostics
Alison K EsserKatherine N Weilbaecher

Abstract

Tumor-associated macrophages (TAMs) enhance tumor growth in mice and are correlated with a worse prognosis for breast cancer patients. While early therapies sought to deplete all macrophages, current therapeutics aim to reprogram pro-tumor macrophages (M2) and preserve those necessary for anti-tumor immune responses (M1). Recent studies have shown that c-MYC (MYC) is induced in M2 macrophages in vitro and in vivo where it regulates the expression of tumor-promoting genes. In a myeloid lineage MYC KO mouse model, MYC had important roles in macrophage maturation and function leading to reduced tumor growth. We therefore hypothesized that targeted delivery of a MYC inhibitor to established M2 TAMs could reduce polarization toward an M2 phenotype in breast cancer models. Methods: In this study, we developed a MYC inhibitor prodrug (MI3-PD) for encapsulation within perfluorocarbon nanoparticles, which can deliver drugs directly to the cytosol of the target cell through a phagocytosis independent mechanism. We have previously shown that M2-like TAMs express significant levels of the vitronectin receptor, integrin β3, and in vivo targeting and therapeutic potential was evaluated using αvβ3 integrin targeted rhodamine-labeled nanoparti...Continue Reading

Citations

Oct 22, 2020·International Journal of Molecular Sciences·Erna Marija MeškytėYari Ciribilli
Dec 19, 2020·Biomedicines·Saffiya HabibMoganavelli Singh
Apr 1, 2021·Molecular Cancer Therapeutics·Gregory C FoxKatherine N Weilbaecher
Sep 3, 2021·International Journal of Nanomedicine·Lu TangZihao Cai

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Datasets Mentioned

BETA
GSE117970

Methods Mentioned

BETA
ELISA
transgenic
flow cytometry
RNAseq
PCR

Software Mentioned

FlowJo
Prism
Living
Image
GraphPad
Prism8

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