Cepharanthine loaded nanoparticles coated with macrophage membranes for lung inflammation therapy

Abstract

Acute lung injury (ALI) is a disease associated with suffering and high lethality, but to date without any effective pharmacological management in the clinic. In the pathological mechanisms of ALI, a strong inflammatory response plays an important role. Herein, based on macrophage ‘homing’ into inflammation sites and cell membrane coating nanotechnology, we developed a biomimetic anti-inflammation nanosystem (MM-CEP/NLCs) for the treatment of ALI. MM-CEP/NLCs were made with nanostructured lipid carriers (NLCs) coated with natural macrophage membranes (MMs) to achieve effective accumulation of cepharanthine (CEP) in lung inflammation to achieve the effect of treating ALI. With the advantage of suitable physicochemical properties of NLCs and unique biological functions of the macrophage membrane, MM-CEP/NLCs were stabilized and enabled sustained drug release, providing improved biocompatibility and long-term circulation. In vivo , the macrophage membranes enabled NLCs to be targeted and accumulated in the inflammation sites. Further, MM-CEP/NLCs significantly attenuated the severity of ALI, including lung water content, histopathology, bronchioalveolar lavage cellularity, protein concentration, and inflammation cytokines. Our results provide a bionic strategy via the biological properties of macrophages, which may have greater value and application prospects in the treatment of inflammation.

Activatable “Matryoshka” nanosystem delivery NgBR siRNA and control drug release for stepwise therapy and evaluate drug resistance cancer

“…We also test the membrane biological property of the nanosystem [ 72 , 73 ]. As it is displayed in Figure S9 (Supporting Information), the MONCs and MONC-PPG nanosystem exhibited comparable hemolysis with the control group, indicating good biocompatibility.…”

COVID-19 inflammation and implications in drug delivery

“…Under inflammatory conditions, leukocytes, composed of monocytes, lymphocytes, and granulocytes (neutrophils, basophils, and eosinophils) [ 116 ], are recruited from the bloodstream to the inflammation tissue by interactions between their surface proteins (i.e., VLA-4, LFA-1, Mac-1) and the adhesion molecules of activated endothelial cells (i.e., VCAM-1, ICAM-1, PECAM-1 receptors) [ 117 , 118 ]. Therefore, leukocyte-derived membranes have been utilized to endow their cargo with an active targeting to inflammatory sites against different diseases-associated inflammation, especially SARS-CoV-2 ( Table 3 ) [ [119] , [120] , [121] , [122] , [123] , [124] ]. Additionally, they can protect the DDS from RES clearance by extending its lifetime.…”

“… Prolonged circulation and efficient homing to the injured lung resulting in improved attenuation of LPS-induced inflammation was assured by the biomimetic shell. [ 121 ] Neutrophils (DMSO-activated HL-60 cells) None TPCA-1 ~200 nm −16 mV LPS-induced ALI Selective delivery of the anti-inflammatory drug to the injured tissues was assured by interactions between ICAM-1 upregulated on activated endothelial cells and the integrin β2 expressed on neutrophils nanovesicles. [ 122 ] Neutrophils (DMSO-activated HL-60 cells) None Piceatannol ~200 nm −18 mV LPS-induced ALI [ 123 ] Genetically modified leukocytes (leukemia cells C1498) PLGA NPs Dexamethasone 175 nm −20 mV LPS-induced ALI Selective delivery of dexamethasone to the injured tissues was assured by interactions between VCAM-1 overexpressed on inflamed endothelial cells and VLA-4 of the leukocyte membrane.…”

Macrophage Polarization as a Facile Strategy to Enhance Efficacy of Macrophage Membrane‐Coated Nanoparticles in Osteoarthritis

“…Various immune cells, such as the neutrophils and macrophages, have been harnessed for the synthesis of membrane‐coated NPs and demonstrated efficacy for neutralization of inflammatory cytokines in the treatment of inflammatory diseases, such as rheumatoid arthritis, [ 8 ] renal ischemia‐reperfusion injury, [ 9 ] acute pancreatitis, [ 10 ] ulcerative colitis, [ 11 ] atherosclerosis, [ 12 ] and acute lung injury. [ 13 ]…”

“…Various immune cells, such as the neutrophils and macrophages, have been harnessed for the synthesis of membrane-coated NPs and demonstrated efficacy for neutralization of inflammatory cytokines in the treatment of inflammatory diseases, such as rheumatoid arthritis, [8] renal ischemiareperfusion injury, [9] acute pancreatitis, [10] ulcerative colitis, [11] atherosclerosis, [12] and acute lung injury. [13] These prior work inspired us to develop cell membrane-coated NPs as a broad-spectrum anti-inflammatory agent to overcome the complexity of OA inflammation driven by a plethora of inflammatory mediators. Among the immune cells implicated in OA inflammation, macrophages represent one of the prominent innate immune cell types that rapidly infiltrate the inflamed synovium in early OA, mediating joint inflammation and tissue damage.…”