Organelle-Targeted Liposome System Design

• Mitochondria: Lipid-anchored cations like triphenylphosphonium accumulate payloads by leveraging the mitochondrial membrane potential.
• Lysosome: Weak-base motifs such as morpholine and mannose-6-phosphate (M6P) conjugates exploit acid trapping or receptor-mediated uptake.
• Nucleus: NLS-bearing peptides guide liposomes through the nuclear pore complex when size and timing are optimized.
• ER/Golgi: ER-retention sequences and small-molecule Golgi probes are adapted into conjugation scaffolds to direct liposomes to these compartments.

Ligands are installed by orthogonal chemistries—maleimide–thiol coupling, copper-free click chemistry (SPAAC), or CuAAC under chelated conditions—balancing conjugation yield, ligand orientation, and membrane integrity.

• Stimuli-responsive bilayers: DOPE/CHEMS compositions destabilize in acidic compartments, accelerating release.
• Endosomal escape boosters: Fusogenic peptides and buffering lipopolymers help transfer cargo into the cytosol before organelle entry.
• Cargo matching: Hydrophilic payloads use aqueous core loading, hydrophobic compounds partition into the bilayer, and sensitive macromolecules may require cleavable linkers.

Creative Biolabs doesn’t stop at uptake. We quantify organelle targeting with confocal colocalization (Pearson’s and Manders’ coefficients with thresholding controls) and subcellular fractionation followed by western blotting against canonical markers (e.g., COX IV for mitochondria; LAMP1 for lysosome; calnexin for ER; GM130 for Golgi; histone H3 for nucleus).