Inhaled Macrophage Apoptotic Bodies-Engineered Microparticle Enabling Construction of Pro-Regenerative Microenvironment to Fight Hypoxic Lung Injury in Mice.

Oxygen therapy cannot rescue local lung hypoxia in patients with severe respiratory failure. Here, an inhalable platform is reported for overcoming the aberrant hypoxia-induced immune changes and alveolar damage using camouflaged poly(lactic-co-glycolic) acid (PLGA) microparticles with macrophage apoptotic body membrane (cMAB). cMABs are preloaded with mitochondria-targeting superoxide dismutase/catalase nanocomplexes (NCs) and modified with pathology-responsive macrophage growth factor colony-stimulating factor (CSF) chains, which form a core-shell platform called C-cMAB/NC with efficient deposition in deeper alveoli and high affinity to alveolar epithelial cells (AECs) after CSF chains are cleaved by matrix metalloproteinase 9. Therefore, NCs can be effectively transported into mitochondria to inhibit inflammasome-mediated AECs damage in mouse models of hypoxic acute lung injury. Additionally, the at-site CSF release is sufficient to rescue circulating monocytes and macrophages and alter their phenotypes, maximizing synergetic effects of NCs on creating a pro-regenerative microenvironment that enables resolution of lung injury and inflammation. This inhalable platform may have applications to numerous inflammatory lung diseases.

Tumor polyamines as guest cues attract host-functionalized liposomes for targeting and hunting via a bio-orthogonal supramolecular strategy.

Inspired by the attractions of fruit flies to polyamines of rotten food, we developed a facile, bio-orthogonal, supramolecular homing and hunting strategy, relying on the elevated levels of polyamines in tumor as the natural guest cues to attract cucurbit [7] uril (CB[7]) functionalized liposomes to the tumor site, owing to the strong, bio-orthogonal host-guest interactions between CB[7] and polyamines. This supramolecular homing enabled a high targeting efficiency of CB[7] functionalized liposomes, and allowed better tissue penetration and retention in breast tumor. The employment of a receptor functionalized nanomedicine for direct tropism towards endogenous biomarkers as guest cues, reminiscent of natural chemotaxis but in a bio-orthogonal manner, has not been previously reported, offering new sights to the design and development of new nanoformulations that rely on bio-orthogonal interactions for chemotaxis-guided targeting.

Cryo-Shocked Platelet Coupled with ROS-Responsive Nanomedicine for Targeted Treatment of Thromboembolic Disease.

Thrombolysis with tissue plasminogen activator (tPA) provides the most common therapy for ischemic stroke onset within the past 4.5 h. However, enhanced neutrophil infiltration and secondary blood-brain barrier injury caused by tPA administration have limited its therapeutic application, and tPA treatment is often accompanied by hemorrhagic transformation. To overcome the limitations of thrombolysis by tPA, maximize the therapeutic efficacy, and improve the safety, herein, we report a cryo-shocked platelet-based cell-hitchhiking drug delivery system, which consists of cryo-shocked platelet (CsPLT) and reactive oxygen species (ROS)-responsive liposomes loaded with thrombolytic tPA and anti-inflammation drug aspirin (ASA). CsPLT and liposomes were facilely conjugated via host-guest interactions. Under the guidance of CsPLT, it selectively accumulated in the thrombus site and quickly released the therapeutic payloads in response to the high ROS. tPA subsequently exhibited localized thrombolytic activity to suppress the expansion of thrombus, while ASA assisted in the inactivation of reactive astrogliosis, microglial/macrophage, and obstruction of neutrophil infiltration. This cryo-shocked platelet-hitchhiking tPA/ASA delivery system not only improves the thrombus-targeting efficiency of the two drugs for highly localized thrombolytic effects and anti-inflammation actions and platelets inactivation but also provides insights to the development of targeted drug delivery systems for thromboembolic disease treatment.