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Different techniques developed for the encapsulation of biological drugs within polymeric nanoparticles.

Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory syndrome coronavirus 2 (SARs-CoV2), thus decrease infection, would be of high relevance to cardiovascular disease, diabetes and SARs-CoV2 infection. While the need for such a drug lead was highlighted over a decade ago receiving over 600 citations,1 to date, no such drugs are available.2 Here, we report the development of a novel ACE2 stimulator, designated ‘2A’(international PCT filed), which is a 10 amino acid peptide derived from a snake venom, and demonstrate its in vitro and in vivo efficacy against SARs-CoV2 infection and associated lung inflammation. Peptide 2A also provides remarkable protection against glycaemic dysregulation, weight loss and disease severity in a mouse model of type 1 diabetes. No untoward effects of 2A were observed in these pre-clinical models suggesting its strong clinical translation potential.

We have for the first time reported 120 nm silver/iron oxide hybrid nano-popcorns with surface plasmon resonance tuned at near-infrared (NIR) range for imaging and therapeutic applications. The nano-popcorns displayed excellent photothermal thrombolytic effect and anticancer activity in a concentration-dependent manner upon NIR laser irradiation, benefiting the photothermal treatment of thrombosis and cancer. At low concentrations, the nano-popcorns exhibited relatively good reactive oxygen species (ROS) scavenging capability. Notably, the nano-popcorns exerted excellent magnetic resonance imaging (MRI) T2-signal after being sequestered within cells or binding on the surface of the thrombus, becoming a promising imaging agent for cell labeling and thrombus detection. Cytotoxicity, biodistribution studies, and histology analysis demonstrated no significant toxicity caused by the nano-popcorns. There was no long-term retention of the nano-popcorns in the mouse organs at the dose treated. These results give insight into the potential of using these nano-popcorns for diagnosis and treatment of diseases related to ROS, cancer, and thrombosis.

Overproduction of reactive oxygen species (ROS) is commonly known as a key factor in the progression of many chronic inflammation diseases such as atherosclerosis and rheumatoid arthritis. In this study, a metal oxide nanodot-coated layered double hydroxide (LDH) nanocomposite is constructed for theranostics of ROS-related diseases. This is the first time that both cerium oxide and iron oxide nanoparticles (NPs) were attached on the surface of LDH NPs through electrostatic interaction via a nanoengineering approach. LDHs served as nanocarriers, cerium oxide NPs served as therapeutic agents due to the antioxidant properties, and iron oxide NPs served as magnetic resonance imaging (MRI) contrast agents. In vitro studies have demonstrated that the constructed nanocomposites have good biocompatibility, good antioxidant capacity to reduce ROS level in the cells, as well as satisfying cell imaging effect in MRI. Functionalization of LDH surface with cerium oxide NPs and iron oxide NPs allows the simultaneous therapy and diagnosis of ROS-related diseases and may also allow biodistribution tracking of the therapeutic cerium oxide NPs.

In this study, modular two-in-one nano-cocktails were synthesised to provide treatment of inflammatory diseases and also enable tracking of their delivery to the disease sites. Chitosan nano-cocktails loaded with treatment module (cerium oxide nanoparticles) and imaging module (iron oxide nanoparticles) were synthesised by electrostatic self-assembly (Chit-IOCO) and ionic gelation method (Chit-TPP-IOCO), respectively. Their MRI capability, anti-inflammatory and anti-fibrosis ability were investigated. Results demonstrated that Chit-IOCO significantly reduced the expression of TNF-α and COX-2, while Chit-TPP-IOCO reduced IL-6 in the LPS-stimulated macrophages RAW264.7. Cytotoxicity studies showed that the nano-cocktails inhibited the proliferation of macrophages. Additionally, Chit-IOCO exhibited higher in vitro MRI relaxivity than Chit-TPP-IOCO, indicating that Chit-IOCO is a better MRI contrast agent in macrophages. It was possible to track the delivery of Chit-IOCO to the inflamed livers of CCl4-treated C57BL/6 mice, demonstrated by a shortened T2⁎ relaxation time of the livers after injecting Chit-IOCO into mice. In vivo anti-inflammatory and blood tests demonstrated that Chit-IOCO reduced inflammation-related proteins (TNF-a, iNOS and Cox-2) and bilirubin in CCl4 treated C57BL/6. Histology images indicated that the nano-cocktails at the treatment doses did not affect the organs of the mice. Importantly, the nano-cocktail reduced fibrosis of CCl4-treated mouse liver. This is the first reported data on the anti-inflammation and anti-fibrosis efficacy of Chit-IOCO in C57BL/6 mouse liver inflammation model. Overall, Chit-IOCO nanoparticles have shown great potential in MR imaging/detecting and treating/therapeutic capabilities for inflammatory diseases.