pHLIC technology constitutes family of pH-Low Insertion Cycles (cyclic peptides), a novel class of pH-sensitive delivery agents, which selectively target and intracellularly deliver diagnostic and therapeutic molecules to inflamed tissues including neuroinflammation. pHLICs are 8-12 aa cyclic peptides with protonatable Glu residues and Trp residues at different side of a cycle. At the normal pH, Glu residues are negatively-charged (red circles) and Trp residues (green circles) interact with headgroups of bilayer. The concentration ratio of pHLICs on inner and outer leaflets at pHsurf = 7.4 and pHin = 7.2 (normal cells) is about 0.6. A drop of a pH leads to the protonation of Glu residues (blue circles), which enhances peptides hydrophobicity and induces partition into the bilayer, The concentration ratio of pHLICs on inner and outer leaflets at pHsurf = 6.0 and pHin = 7.2 (metabolically active cells) is about 11 for the selected cyclic peptide.