Transmembrane mechanisms and targeted delivery strategies of self-assembling peptides in tumor therapy

Self-assembling peptides have been widely used in biomedical fields due to their remarkable advantages including excellent biocompatibility and biodegradable, as well as distinctive physicochemical and biochemical activities. To enabling the further widespread application of self-assembling peptides (SAPs) in clinical cancer therapies, this review summarizes the transmembrane mechanisms and targeted delivery strategies of self-assembling peptides nanomedicines. There are six primary types of transmembrane mechanisms involved in SAPs nanomedicines: classical endocytosis, fluoride-modified transmembrane transport, macropinocytosis-mediated transmembrane transport, flexible cyclic peptide-mediated transmembrane transport, receptor-mediated transmembrane transport, and cell-penetrating peptide-mediated endocytosis. The specific delivery of such systems is mainly determined by the incorporated targeting peptides including three types: tumor cell-targeting peptides, tumor vascular endothelial cell-targeting peptides and tumor microenvironment-targeting peptides. Additionally, in the perspective, we highlight the state-of-the-art design and fabrication of SAPs, and put forward our viewpoints on their future development in cancer therapy and the potential challenges in their clinical translation.