No abstract

Monocytes participate critically in atherosclerosis. There are 2 major subsets expressing different chemokine receptor patterns: CCR2 + CX3CR1 + Ly-6C hi and CCR2 -CX3CR1 ++ Ly-6C lo monocytes. Both C-C motif chemokine receptor 2 (CCR2) and C-X 3 -C motif chemokine receptor 1 (CX3CR1) are linked to progression of atherosclerotic plaques. Here, we analyzed mouse monocyte subsets in apoE-deficient mice and traced their differentiation and chemokine receptor usage as they accumulated within atherosclerotic plaques. Blood monocyte counts were elevated in apoE -/-mice and skewed toward an increased frequency of CCR2 + Ly-6C hi monocytes in apoE -/-mice fed a high-fat diet. CCR2 + Ly-6C hi monocytes efficiently accumulated in plaques, whereas CCR2 -Ly-6C lo monocytes entered less frequently but were more prone to developing into plaque cells expressing the dendritic cell-associated marker CD11c, indicating that phagocyte heterogeneity in plaques is linked to distinct types of entering monocytes. CCR2 -monocytes did not rely on CX3CR1 to enter plaques. Instead, they were partially dependent upon CCR5, which they selectively upregulated in apoE -/-mice. By comparison, CCR2 + Ly-6C hi monocytes unexpectedly required CX3CR1 in addition to CCR2 and CCR5 to accumulate within plaques. In many other inflammatory settings, these monocytes utilize CCR2, but not CX3CR1, for trafficking. Thus, antagonizing CX3CR1 may be effective therapeutically in ameliorating CCR2 + monocyte recruitment to plaques without impairing their CCR2-dependent responses to inflammation overall.

No abstract

Some monocytes normally take up residence in tissues as sessile macrophages, but others differentiate into migratory cells resembling dendritic cells that emigrate to lymph nodes. In an in vitro model of a vessel wall, lipid mediators lysophosphatidic acid and platelet-activating factor, whose signals are implicated in promoting atherosclerosis, blocked conversion of monocytes into migratory cells and favored their retention in the subendothelium. In vivo studies revealed trafficking of monocyte-derived cells from atherosclerotic plaques during lesion regression, but little emigration was detected from progressive plaques. Thus, progression of atherosclerotic plaques may result not only from robust monocyte recruitment into arterial walls but also from reduced emigration of these cells from lesions.

Despite regulation of the reactive oxygen species (ROS) level is an intelligent strategy for cancer therapy, the therapeutic effects of ROS-mediated therapy (including photodynamic therapy (PDT) and chemodynamic therapy (CDT)) are limited by oxygen reliance, inherent flaws of traditional photosensitizers, and strict reaction conditions of effective Fenton reaction. Herein, we reported biocompatible copper ferrite nanospheres (CFNs) with enhanced ROS production under irradiation with a 650 nm laser through direct electron transfer and photoenhanced Fenton reaction and high photothermal conversion efficiency upon exposure to an 808 nm laser, exhibiting a considerable improved synergistic treatment effect. Importantly, by exploiting the properties of O generation and glutathione (GSH) depletion of CFNs, CFNs relieve the hypoxia and antioxidant capability of the tumor, achieving photoenhanced CDT and improved PDT. The high relaxivity of 468.06 mM s enables CFNs to act as an outstanding contrast agent for MRI in vitro and in vivo. These findings certify the potential of such "all in one" nanotheranostic agent integrated PDT, photoenhanced CDT, photothermal therapy (PTT), and MRI imaging capabilities along with modulating the tumor microenvironment function in theranostics of cancer.