In murine immunocompetent models of estrogen receptor positive (ER+) and triple-negative breast cancers, αvβ3-targeted MI3 prodrug nanoparticles (αvβ3-MI3-PD NP) decreased M2 polarized TAMs in mammary fat pad tumors and preserved M1 TAM numbers. The gene discussed is ESR1; the disease is triple-negative breast carcinoma.