Imaging Identifies Superior Inflammation Targeting of M1 Macrophages for Cryo-Shocked Cell Pulmonary Drug Delivery to Treat Acute Lung Injury.

In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo-shocked macrophages, tailored for pulmonary drug delivery. Positron emission tomography (PET) imaging has shed light on the remarkable targeting abilities of live M1 macrophages, showcasing their unparalleled efficacy in homing in on local inflammatory foci when contrasted with naive, M1, and M2 macrophages. Building upon this foundation, liquid nitrogen-treated (LNT) M1 macrophages are developed, engineered to preserve their inflammation-targeting prowess while sidestepping the release of pro-inflammatory cytokines. This breakthrough allows for the delivery of glucocorticoids directly to inflamed lung tissues, efficiently quelling inflammation and mitigating pulmonary edema while drastically reducing systemic drug exposure. Inspired by the effectiveness of live M1 macrophages, the potential of glucocorticoid-loaded LNT M1 macrophages are harnessed, utilizing them as a stealthy "Trojan horse" in the battle against pneumonia-induced ALI. This innovative approach holds promise as a safe and potent treatment avenue for acute lung injury.

Rectal delivery of 89Zr-labeled infliximab-loaded nanoparticles enables PET imaging-guided localized therapy of inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) like Crohn's disease and ulcerative colitis involve chronic gastrointestinal inflammation. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) drives IBD pathogenesis. Anti-TNF-α therapies using monoclonal antibodies (mAbs) like infliximab (INF) help treat IBD but have limitations. We developed inflammation-targeting polyphenol-poloxamer nanoparticles loaded with the anti-inflammatory mAb INF (INF@PPNP) as a novel IBD therapy. Characterization showed that INF@PPNP had favorable stability and purity. Radiolabeling INF@PPNP with 89Zr enabled tracking localization with positron emission tomography (PET) imaging. Rectal administration of 89Zr-INF@PPNP led to colon delivery with remarkably reduced systemic exposure versus intravenous INF revealed by non-invasive PET imaging. 89Zr-INF@PPNP retention at inflamed foci indicated prolonged INF@PPNP action. INF@PPNP rectally achieved similar anti-inflammatory effects as intravenously injected INF, demonstrating the high therapeutic potential. Our findings support the use of nanoparticle-based rectal administration for localized drug delivery, prolonging drug activity and minimizing systemic exposure, ultimately offering an effective approach for treating IBD.

Radiolabelling and in vivo radionuclide imaging tracking of emerging pollutants in environmental toxicology: A review.

Emerging pollutants (EPs) have become a global concern, attracting tremendous attention because of serious threats to human and animal health. EP diversity emanates from their behaviour and ability to enter the body via multiple pathways and exhibit completely different distribution, transport, and excretion. To better understand the in vivo behaviour of EPs, we reviewed radiolabelling and in vivo radionuclide imaging tracking of various EPs, including micro- and nano-plastics, perfluoroalkyl substances, metal oxides, pharmaceutical and personal care products, and so on. Because this accurate and quantitative imaging approach requires the labelling of radionuclides onto EPs, the main strategies for radiolabelling were reviewed, such as synthesis with radioactive precursors, element exchange, proton beam activation, and modification. Spatial and temporal biodistribution of various EPs was summarised in a heat map, revealing that the absorption, transport, and excretion of EPs are markedly related to their type, size, and pathway into the body. These findings implicate the potential toxicity of diverse EPs in organs and tissues. Finally, we discussed the potential and challenges of radionuclide imaging tracking of EPs, which can be considered in future EPs studies.

Recent advances in electrochemical proximity ligation assay.

Proximity ligation assay (PLA) is a vigorously developed homogeneous immunoassay assisted by DNA combining dual recognition of target protein by pairs of proximity probes, in which the detection of protein is tactfully converted to the detection of DNA. The booming developments in PLA have enabled a variety of ultrasensitive assays for the detection of protein and this concept of PLA is also extended to the detection of nucleic acids and some small molecule. The association between PLA and electrochemical method, defined as electrochemical proximity ligation assay (ECPLA), has gained much interests in disease diagnosis, food safety and environmental assays with the advantages, such as broad range of targets, simplicity, low cost and rapid response. In this review, we took a different perspective to present the history of PLA, the classical ECPLA biosensing methodology as well as the developments of ECPLA based on several key parameters, such as sensitivity, selectivity, reusability and generalization. In addition, the developments of PLA with electrochemiluminescence as readout are also presented. Finally, perspective and some unresolved challenges in ECPLA that can potentially be addressed have also been discussed.

Immuno-PET Imaging of TNF-α in Colitis Using 89Zr-DFO-infliximab.

Tumor necrosis factor-alpha (TNF-α) neutralization has become increasingly important in the treatment of inflammatory bowel diseases (IBD). A series of monoclonal antibodies were approved in the clinic for anti-TNF-α therapy. However, a comprehensive assessment of TNF-α levels throughout the colon, which facilitates the diagnosis of IBD and predicts anti-TNF-α efficacy, remains challenging. Here, we radiolabeled infliximab with long-lived radionuclides 89Zr for immuno-positron emission tomography (PET) imaging of TNF-α in vivo. The increased TNF-α level was detected in the inflammatory colon of the dextran sodium sulfate-induced colitis mice. The immuno-PET imaging of 89Zr-desferrioxamine-infliximab reveals a high uptake (7.1 ± 0.3%ID/g) in the inflammatory colon, which is significantly higher than in the healthy control and blocked groups. The colon-to-muscle ratio reached more than 10 and was maintained at a high level for 10 h after injection. The ex vivo biodistribution study also verified the superior uptake in the inflammatory colon. This study provides an in vivo immune-PET approach to molecular imaging of the pro-inflammatory cytokine TNF-α. It is promising in diagnosing and predicting efficacy in both IBD and other autoimmune diseases.

Hole Transport in Low-Donor-Content Organic Solar Cells.

Organic solar cells with an electron donor diluted in a fullerene matrix have a reduced density of donor-fullerene contacts, resulting in decreased free-carrier recombination and increased open-circuit voltages. However, the low donor concentration prevents the formation of percolation pathways for holes. Notwithstanding, high (>75%) external quantum efficiencies can be reached, suggesting an effective hole-transport mechanism. Here, we perform a systematic study of the hole mobilities of 18 donors, diluted at ∼6 mol % in C60, with varying frontier energy level offsets and relaxation energies. We find that hole transport between isolated donor molecules occurs by long-range tunneling through several fullerene molecules, with the hole mobilities being correlated to the relaxation energy of the donor. The transport mechanism presented in this study is of general relevance to bulk heterojunction organic solar cells where mixed phases of fullerene containing a small fraction of a donor material or vice versa are present as well.

Ultrafast Long-Range Charge Separation in Nonfullerene Organic Solar Cells.

Rapid, long-range charge separation in polymer-fullerene organic solar cells (OSCs) enables electrons and holes to move beyond their Coulomb capture radius and overcome geminate recombination. Understanding the nature of charge generation and recombination mechanisms in efficient, nonfullerene-acceptor-based OSCs are critical to further improve device performance. Here we report charge dynamics in an OSC using a perylene diimide (PDI) dimer acceptor. We use transient absorption spectroscopy to track the time evolution of electroabsorption caused by the dipolar electric field generated between electron-hole pairs as they separate after ionization at the donor-acceptor interface. We show that charges separate rapidly (<1 ps) and that free charge carriers are generated very efficiently (∼90% quantum yield). However, in the PDI-based OSC, external charge extraction is impaired by faster nongeminate decay to the ground state and to lower-lying triplet states.

Absorption Tails of Donor:C60 Blends Provide Insight into Thermally Activated Charge-Transfer Processes and Polaron Relaxation.

In disordered organic semiconductors, the transfer of a rather localized charge carrier from one site to another triggers a deformation of the molecular structure quantified by the intramolecular relaxation energy. A similar structural relaxation occurs upon population of intermolecular charge-transfer (CT) states formed at organic electron donor (D)-acceptor (A) interfaces. Weak CT absorption bands for D-A complexes occur at photon energies below the optical gaps of both the donors and the C60 acceptor as a result of optical transitions from the neutral ground state to the ionic CT state. In this work, we show that temperature-activated intramolecular vibrations of the ground state play a major role in determining the line shape of such CT absorption bands. This allows us to extract values for the relaxation energy related to the geometry change from neutral to ionic CT complexes. Experimental values for the relaxation energies of 20 D:C60 CT complexes correlate with values calculated within density functional theory. These results provide an experimental method for determining the polaron relaxation energy in solid-state organic D-A blends and show the importance of a reduced relaxation energy, which we introduce to characterize thermally activated CT processes.

Comparison of the Optical and Electrochemical Properties of Bi(perylene diimide)s Linked through Ortho and Bay Positions.

The Ullmann homocoupling of 2-bromo-perylene diimides (PDIs) gave [2,2'-biperylene]-3,4:9,10:3',4':9',10'-tetrakis(dicarboximide)s, 2,2'-bi(PDI)s, and the Suzuki coupling of a PDI-2-boronic ester and a 1-bromo-PDI gave a [1,2'-biperylene]-3,4:9,10:3',4':9',10'-tetrakis(dicarboximide), 1,2'-bi(PDI). These were compared with [1,1'-biperylene]-3,4:9,10:3',4':9',10'-tetrakis(dicarboximide)s, 1,1'-bi(PDI)s. Solution absorption spectra suggest that the PDIs in 2,2'-bi(PDI)s are more planar and less strongly coupled than those in 1,1'-bi(PDI)s, which is consistent with density functional theory calculations. 2,2'-Bi(PDI)s are less easily reduced than 1,1'- and 1,2'-bi(PDI)s by ca. 70-90 mV. Bulk heterojunction organic solar cells incorporating a 2,2'-bi(PDI) acceptor behaved similarly to those employing its 1,1'-bi(PDI) analogue.