For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as "accelerated blood clearance (ABC)" where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe(3)O(4) nanoparticles (Fe(3)O(4) @RBC NPs) rely on CD47, which is a "don't eat me" marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-α) receptor. Fe(3)O(4) @RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe(3)O(4) @RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.

PLA is a renewable, bio-based, and biodegradable aliphatic thermoplastic polyester that is considered a promising alternative to petrochemical-derived polymers in a wide range of commodity and engineering applications.

Inflammatory responses represent a hallmark of numerous pathologies including sepsis, bacterial infection, insulin resistance, and malign obesity. Here we describe an unexpected coactivator function for the nuclear receptor interacting protein 140 (RIP140) for nuclear factor B (NFB), a master transcriptional regulator of inflammation in multiple tissues. Previous work has shown that IntroductionMetabolic diseases, such as insulin resistance, obesity, and atherosclerosis, have recently been recognized as low-grade, subacute inflammatory conditions, contributing to the development of type II diabetes and cardiovascular failure. 1 Similar to acute inflammation, all of these conditions are characterized by elevated levels of proinflammatory cytokines such as interleukin-1␤ (IL-1␤) and IL-6, and tumor necrosis factor ␣ (TNF␣). 2,3 Toward this end, levels of IL-6, IL-1␤, and TNF␣ are elevated in obese patients and mouse models of insulin resistance and obesity. [2][3][4] In this respect, ablation of the TNF␣ gene or of its receptor renders mice resistant to the development of insulin resistance and associated metabolic disorders. 5,6 A common polymorphism has been identified in the IL-6 receptor gene that is associated with energy intake and obesity in humans, 7 underlining the critical impact of cytokine signaling for metabolic diseases.The inflammatory response emerging in the presence of insulin resistance and obesity seems to reside predominantly in adipose tissue. 1,8 Indeed, transgenic overexpression of monocyte chemotactic protein 1 (MCP1) in adipose tissue results in enhanced macrophage infiltration, inflammation, and insulin resistance. 9,10 On the other hand, impairment of macrophage migration into adipose tissue by genetic knockout of the MCP1 receptor chemotactic cytokine receptor 2 (CCR2) has been found to substantially improve tissue inflammation and insulin sensitivity. 10,11 Importantly, macrophages have recently been shown to accumulate under obese conditions in adipose tissue of both mice and humans. 12,13 Resident macrophages in adipose tissue, therefore, seem to be in large part responsible for the cytokine release of this tissue and the systemic inflammation associated with obesity. 12,14 These studies highlighted the importance of adipose tissue as a key site for the interaction of metabolic cells with effectors of the immune system, specifically macrophages, to control systemic energy homeostasis and to trigger metabolic dysfunction under pathophysiologic conditions. 8 Consequently, not only adipose tissue quantity but also quality, as exemplified by its macrophage content and inflammatory status, seems to represent a critical determinant for the onset of insulin resistance and other components of the metabolic syndrome. 8,15 In this respect, the cytokine release from macrophages in response to external signals is largely determined by transcriptional mechanisms. A number of transcriptional regulators have been identified as critical checkpoints for the proinflammatory response of macrophages, ...

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The protumorigenic insulin-like growth factor (IGF)-II is highly expressed in a significant fraction of human hepatocellular carcinomas (HCC).