Precise delivery of doxorubicin and imiquimod through pH-responsive tumor microenvironment-active targeting micelles for chemo- and immunotherapy.

Recently, combining immunotherapy and chemotherapy has become a promising strategy to treat cancer. However, this therapeutic strategy still has its limitations because of the adverse effects caused by the simultaneous administration of multiple therapeutic agents. Using nanoparticles is an effective approach to successfully combine these therapies because they can reduce side effects, increase circulation time, and ensure the delivery of cytotoxic agents to tumor tissues. In this study, dual pH-sensitive and tumor microenvironment (TME)-active targeting micelles comprising poly(propyl methacrylate-co-glucosamine/histidine/doxorubicin) (P(PAA-co-GLU/HIS/DOX) and methoxy-poly(ethylene glycol)-block-poly(l-lysine) were prepared to encapsulate an immunomodulator, imiquimod (IMQ). Because these micelles can expose glucose targeting ligands at the TME and pH-dependently release IMQ and DOX, micelles effectively inhibit the growth of 4T1 cells selectively and highly accumulate in 4T1 cells as the pH decreased to 6.5. Moreover, in RAW 264.7 â€‹cells, these micelles prevent cell death and induce M1 macrophage polarization. In 4T1 orthotopic tumor-bearing mice, micelles not only exhibited high tumor accumulation, effective tumor inhibition, and fewer adverse effects, but also dramatically increased the number of mature dendritic cells, activate cytotoxic T cells, and polarize M1-like macrophages in tumor tissues. Overall, these micelles exhibit precise pH responsiveness and ideal drug delivery capabilities for combined chemo- and immunotherapy; these results significantly contribute to the future development of nanomedicines in cancer therapy.

Nickel-containing nano-sized islands grown on Ge(111)-c(2 × 8) and Ag/Ge(111)-(√3 × âˆš3) surfaces.

The formation of nano-islands on both a Ge(111)-c(2 × 8) surface and an Ag/Ge(111)-(√3 × âˆš3) surface evaporated with 0.1 ML Ni was investigated by scanning tunneling microscopy (STM). We have noticed that at temperatures lower than 670 K, the reaction between Ni and the individual substrate surfaces proceeds to form different structures: flat-topped islands with a 2√7 × 2√7 or a 3 × 3 reconstruction on the Ni/Ge(111)-c(2 × 8) surface vs. islands with a 7 × 7 reconstruction on the Ni/Ag/Ge(111)-(√3 × âˆš3) surface. From this we have inferred that within a temperature range between room temperature and 670 K, the intermediate Ag layer retards mixing between Ni and Ge atoms. As a result, the grown islands are composed of pure Ni atoms. Within a temperature range from 670 to 770 K, most islands produced on the Ag/Ge(111)-(√3 × âˆš3) surface are identical with those formed on the Ni/Ge(111)-c(2 × 8) surface, suggesting that above 670 K, Ni atoms are likely to bind with Ge atoms. However, an essential difference between STM images of the surfaces under study exists in the appearance of large elongated islands on the Ni/Ag/Ge(111)-(√3 × âˆš3) surface. The formation of the latter is explained in terms of a difference in energy for Ni diffusion on the Ge(111)-c(2 × 8) and Ag/Ge(111)-(√3 × âˆš3) surfaces.