Multifunctional nanoparticles based on a polymeric copper chelator for combination treatment of metastatic breast cancer.

Multifunctional nanoparticles based on a polymeric copper chelator for combination treatment of metastatic breast cancer. Biomaterials. 2019 Jan 04;195:86-99 Authors: Zhou P, Qin J, Zhou C, Wan G, Liu Y, Zhang M, Yang X, Zhang N, Wang Y Abstract 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 f...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research