Photodynamic therapy (PDT) is traditionally ineffective for deeply embedded tumors due to the poor penetration depth of the excitation light. Chemiluminescence resonance energy transfer (CRET) has emerged as a promising mode of PDT without external light. To date, related research has frequently used endogenous hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ) inside the solid tumor microenvironment to trigger CRET-mediated PDT. Unfortunately, this significantly restricts treatment efficacy and the development of further biomedical applications because of the limited amounts of endogenous H 2 O 2 and O 2 . Herein, a nanohybrid (mSiO 2 /CaO 2 /CPPO/Ce6: mSCCC) nanoparticle (NP) is designed to achieve synergistic CRET-mediated PDT and calcium (Ca 2+ )-overload-mediated therapy. The calcium peroxide (CaO 2 ) formed inside mesoporous SiO 2 (mSC) with the inclusion of the chemiluminescent agent (CPPO) and photosensitizer (Ce6) self-supplies H 2 O 2 , O 2 , and Ca 2+ allowing for the subsequent treatments. The Ce6 in mSCCC NPs is excited by chemical energy in situ following the supply of H 2 O 2 and O 2 to produce singlet oxygen ( 1 O 2 ). The nanohybrid NPs are coated with stearic acid to avoid decomposition during blood circulation through contact with aqueous environment. This nanohybrid shows promising performance in the generation of 1 O 2 for external light-free PDT and the release of Ca 2+ ions for Ca 2+ -overloaded therapy against orthotopic hepatocellular carcinoma.

Background Late diagnosis of lung cancer is one of the leading causes of higher mortality in lung cancer patients worldwide. Significant research attention has focused on the use of magnetic resonance imaging (MRI) based nano contrast agents to efficiently locate cancer tumors for surgical removal or disease diagnostics. Although contrast agents offer significant advantages, further clinical applications require improvements in biocompatibility, biosafety and efficacy. Results To address these challenges, we fabricated ultra-fine Iron Carbonate Nanoparticles (FeCO3 NPs) for the first time via modified literature method. Synthesized NPs exhibit ultra-fine size (~ 17 nm), good dispersibility and excellent stability in both aqueous and biological media. We evaluated the MR contrast abilities of FeCO3 NPs and observed remarkable T2 weighted MRI contrast in a concentration dependent manner, with a transverse relaxivity (r2) value of 730.9 ± 4.8 mM−1 S−1at 9.4 T. Moreover, the r2 values of present FeCO3 NPs are respectively 1.95 and 2.3 times higher than the clinically approved contrast agents Resovist® and Friedx at same 9.4 T MR scanner. FeCO3 NPs demonstrate an enhanced T2 weighted contrast for in vivo lung tumors within 5 h of post intravenous administration with no apparent systemic toxicity or induction of inflammation observed in in vivo mice models. Conclusion The excellent biocompatibility and T2 weighted contrast abilities of FeCO3 NPs suggest potential for future clinical use in early diagnosis of lung tumors. Graphical Abstract

Background: Histamine exerts diverse effects on immune regulation through four types of histamine receptors (HRs). Among them, type 1 receptor (H1R) plays an important role in allergic inflammation. Dendritic cells (DCs), which express at least three types of HRs, are professional antigen-presenting cells controlling the development of allergic inflammation. However, the molecular mechanisms involved in H1R-mediated NF-ĸB signaling of DCs remain poorly defined. Methods: Bone-marrow (BM)-derived DCs (BM-DCs) were treated with H1R inverse agonists to interrupt basal H1R-mediated signaling. The crosstalk of H1R-mediated signaling and the NF-ĸB pathway was examined by NF-ĸB cellular activity using a luciferase reporter assay, NF-ĸB subunit analysis using Western blotting and TNF-α promoter activity using chromatin immunoprecipitation. Results: Blockage of H1R signaling by inverse agonists significantly inhibited TNF-α and IL-6 production of BM-DCs. H1R-specific agonists were able to enhance TNF-α production, but this overexpression was significantly inhibited by NF-ĸB inhibitor. The H1R inverse agonist ketotifen also suppressed cellular NF-ĸB activity, suggesting crosstalk between H1R and NF-ĸB signaling in DCs. After comprehensive analysis of NF-ĸB subunits, c-Rel protein expression was significantly down-regulated in ketotifen-treated BM-DCs, which led to inhibition of the promoter activity of TNF-α. Finally, adoptive transfer of the ketotifen-treated BM-DCs did not induce significant allergic airway inflammation compared to that of control cells in vivo. Conclusions: Our results suggest that c-Rel controls H1R-mediated proinflammatory cytokine production in DCs. This study provides a potential mechanism of H1R-mediated signaling and NF-ĸB pathway crosstalk in allergic inflammation.

Ineffective site-specific delivery has seriously impeded the efficacy of nanoparticle-based drugs to a disease site. Here, we report the preparation of three different shapes (sphere, scroll, and oblate) to systematically evaluate the impact of the marginative delivery on the efficacy of magnetic resonance (MR) imaging-guided X-ray irradiation at a low dose of 1 Gy. In addition to the shape effect, the therapeutic efficacy is investigated for the first time to be strongly related to the structure effect that is associated with the chemical activity. The enhanced particle–vessel wall interaction of both the flat scroll and oblate following margination dynamics leads to greater accumulation in the lungs, resulting in superior performance over the sphere against lung tumor growth and suppression of lung metastasis. Furthermore, the impact of the structural discrepancy in nanoparticles on therapeutic efficacy is considered. The tetragonal oblate reveals that the feasibility of the charge-transfer process outperforms the orthorhombic scroll and cubic sphere to suppress tumors. Finally, surface area is also a crucial factor affecting the efficacy of X-ray treatments from the as-prepared particles.