Copper plays an important role in
tumor growth and
metastasis.
Copper chelation has been confirmed to be an effective strategy for
breast cancer therapy through antiangiogenesis. In this work, a
copper chelating coil-comb block copolymer RGD-PEG-b-
PGA-g-(TETA-DTC-PHis) (RPTDH) was synthesized and used to prepare nanoparticles for loading
resiquimod (R848), a TLR7 and TLR8 agonist, thus to combine antiangiogenesis and immune activation to treat
breast cancer. RPTDH has strong
copper-chelating ability and could self-assemble to form spherical nanoparticles with significant pH-sensitivity. R848 was efficiently loaded into RPTDH nanoparticles and exhibited greatly accelerated releases in weakly
acid media simulating tumor microenvironment. RPTDH/R848 nanoparticles significantly inhibited the mobility, invasion and vascular tube formation of HUVECs via
copper chelation, demonstrating their strong antiangiogenic activity in vitro. Furthermore, RPTDH/R848 nanoparticles remarkably induced the maturation and activation of human plasmacytoid dendritic CAL-1 cells, indicating their immune-activation ability. In
breast tumor-bearing mice, RPTDH/R848 nanoparticles displayed excellent targeting ability for both primary
breast tumor and lung
metastases, and furthermore dramatically suppressed
tumor growth and
metastasis through
copper deficiency-triggered antiangiogenesis and R848-induced immune activation. In summary, RPTDH/R848 nanoparticles can be used as an therapeutic agent against metastatic
breast cancer through combining antiangiogenesis and immune activation.