2.B.145.  The Peptide-based MacroMolecular Carrier (PbMMC) Family 

Peptides have been applied for the transport of biologically relevant molecules across bilayers (see Pérez-Pérez et al. 2025 for the summary of details and references). Amphiphilic peptides can function as supramolecular carriers for the transport of a wide range of molecular and biomolecular cargos. Cationic amphiphilic peptides, either alone or in combination with lipids or organic polymers, have been applied as suitable templates for the complexation and transport of nucleic acid cargos. The hydrophobic enhancement of a dimer of the TAT peptide drives the cytosolic delivery of functional biomolecules in vitro and in vivo. Arginine-rich peptides have been validated as efficient carriers for proteins in living cells, and polyarginines and peptides derived from a segment of the HIV-1 TAT peptide can adhere to cell membranes and enhance different energy-dependent uptake pathways (e.g., macropinocytosis). Therefore, attenuated cationic lytic peptides have been designed to enhance macromolecular delivery, taking advantage of these types of active mechanisms. Endosome-disruptive cytosolic peptides can also be engineered to trigger the endosomal escape of proteins and antibodies with minimal toxicity. Dynamic covalent modification (e.g., hydrazone) have been used to modify peptide sequences and obtain transient amphiphilic carriers for the efficient and nontoxic delivery of different nucleic acids and proteins.  Liquid droplets from designed amphiphilic peptide sequences have also been shown to enable the efficient transport of a broad range of biomolecular cargos (Pérez-Pérez et al. 2025).

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