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A tetracationic macrocycle can include clinically used photodynamic agents, alleviating their posttreatment phototoxicity and maintaining their photodynamic efficacy.

Bacterial lipopolysaccharides (LPS, endotoxins) cause sepsis that is responsible for a huge amount of mortality globally. However, their neutralization or detoxification remains an unmet medical need. We envisaged that cationic organic frameworks with persistent hydrophobic porosity may adsorb and thus neutralize LPS through a combination of cooperative ion-pairing electrostatic attraction and hydrophobicity. We here report the preparation of two water-soluble flexible organic frameworks (FOF-1 and FOF-2) from tetratopic and ditopic precursors through quantitative formation of hydrazone bonds at room temperature. The two FOFs are revealed to possess hydrodynamic diameters, which range from 20 to 120 nm, depending on the concentrations. Dynamic light scattering and isothermal titration calorimetric and chromogenic limulus amebocyte lysate experiments indicate that both frameworks are able to adsorb and thus reduce the concentration of free LPS molecules in aqueous solution, whereas cytokine inhibition experiments with RAW264.7 support that this adsorption can significantly decrease the toxicity of LPS. In vivo experiments with mice (five males per group) show that the injection of FOF-1 at a dose of 0.6 mg/kg realizes the survival of all of the mice administrated with LPS of the d-galactosamine (d-Gal)-sensitized absolute lethal dose (LD