Macrophage membrane coated nanoparticles: a biomimetic approach for enhanced and targeted delivery

The enhanced and targeted drug delivery with low systemic toxicity and subsequent release of drugs is the major concern among researchers and pharmaceutics. Inspite of greater advancement and discoveries in...

Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis

Background Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis. Results Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. Conclusion Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty. Graphical Abstract

Macrophage membrane camouflaged reactive oxygen species responsive nanomedicine for efficiently inhibiting the vascular intimal hyperplasia

Background Intimal hyperplasia caused by vascular injury is an important pathological process of many vascular diseases, especially occlusive vascular disease. In recent years, Nano-drug delivery system has attracted a wide attention as a novel treatment strategy, but there are still some challenges such as high clearance rate and insufficient targeting. Results In this study, we report a biomimetic ROS-responsive MM@PCM/RAP nanoparticle coated with macrophage membrane. The macrophage membrane with the innate “homing” capacity can superiorly regulate the recruitment of MM@PCM/RAP to inflammatory lesion to enhance target efficacy, and can also disguise MM@PCM/RAP nanoparticle as the autologous cell to avoid clearance by the immune system. In addition, MM@PCM/RAP can effectively improve the solubility of rapamycin and respond to the high concentration level of ROS accumulated in pathological lesion for controlling local cargo release, thereby increasing drug availability and reducing toxic side effects. Conclusions Our findings validate that the rational design, biomimetic nanoparticles MM@PCM/RAP, can effectively inhibit the pathological process of intimal injury with excellent biocompatibility. Graphical Abstract

Macrophage-Biomimetic Porous Se@SiO2 Nanocomposites For “Dual Model” Immunotherapy Against Inflammatory Osteolysis

Background：Inflammatory osteolysis is a major complication of total joint replacement surgery that can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of pro-inflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (Porous Se@SiO2 nanospheres) for the management of inflammatory osteolysis. Results: Macrophage-membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) can attenuate lipopolysaccharide (LPS)-induced inflammatory osteolysis by a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduce toxin levels and neutralize pro-inflammatory cytokines. Moreover, the release of Se can induce the polarization of macrophages toward the anti-inflammatory M2-phenotype. These effects are mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase(ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduces the inhibition of osteogenic differentiation caused by pro-inflammation cytokines, confirmed through in vitro and in vivo experiments.Conclusion: Our findings suggest that M-Se@SiO2 has an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 is a promising engineered nano-platform for the treatment of osteolysis arising after arthroplasty.

Lure-and-kill macrophage nanoparticles alleviate the severity of experimental acute pancreatitis

Acute pancreatitis is a disease associated with suffering and high lethality. Although the disease mechanism is unclear, phospholipase A2 (PLA2) produced by pancreatic acinar cells is a known pathogenic trigger. Here, we show macrophage membrane-coated nanoparticles with a built-in ‘lure and kill’ mechanism (denoted ‘MΦ-NP(L&K)’) for the treatment of acute pancreatitis. MΦ-NP(L&K) are made with polymeric cores wrapped with natural macrophage membrane doped with melittin and MJ-33. The membrane incorporated melittin and MJ-33 function as a PLA2 attractant and a PLA2 inhibitor, respectively. These molecules, together with membrane lipids, work synergistically to lure and kill PLA2 enzymes. These nanoparticles can neutralize PLA2 activity in the sera of mice and human patients with acute pancreatitis in a dose-dependent manner and suppress PLA2-induced inflammatory response accordingly. In mouse models of both mild and severe acute pancreatitis, MΦ-NP(L&K) confer effective protection against disease-associated inflammation, tissue damage and lethality. Overall, this biomimetic nanotherapeutic strategy offers an anti-PLA2 treatment option that might be applicable to a wide range of PLA2-mediated inflammatory disorders.