Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

Abstract

Mitochondria are well known to serve as the powerhouse for cells and also the initiator for some vital signaling pathways. A variety of diseases are discovered to be associated with the abnormalities of mitochondria, including cancers. Thus, targeting mitochondria and their metabolisms are recognized to be promising for cancer therapy. In recent years, great efforts have been devoted to developing mitochondria-targeted pharmaceuticals, including small molecular drugs, peptides, proteins, and genes, with several molecular drugs and peptides enrolled in clinical trials. Along with the advances of nanotechnology, self-assembled peptide-nanomaterials that integrate the biomarker-targeting, stimuli-response, self-assembly, and therapeutic effect, have been attracted increasing interest in the fields of biotechnology and nanomedicine. Particularly, in situ mitochondria-targeted self-assembling peptides that can assemble on the surface or inside mitochondria have opened another dimension for the mitochondria-targeted cancer therapy. Here, we highlight the recent progress of mitochondria-targeted peptide-nanomaterials, especially those in situ self-assembly systems in mitochondria, and their applications in cancer treatments.

Nanoparticle‐based therapeutic strategies for mitochondrial dysfunction in cardiovascular disease

“…The therapeutic and/or targeting peptides for mitochondria can be further modified to form amphiphiles and self-assemble into various nanostructures. 100 One advantage of self-assembling peptides is that they are dynamic and can be assembled by noncovalent bonds, and their morphology can be tuned. 6C).…”

“…Over the last two decades, several types of mitochondria‐targeted peptides have been discovered (Figure 6A). 100 These molecules usually bear positive charge and target mitochondria due to the negative membrane potential. Mitochondria targeted peptides (mitochondriotropic peptides), such as Szeto‐Schiller (SS) peptides 101 and mitochondria penetrating peptides (MPPs), usually consist of positively charged and hydrophobic amino acids, which interact with phospholipids on mitochondrial inner membranes 102 .…”

Elevating the significance of legume intake: A novel strategy to counter aging‐related mitochondrial dysfunction and physical decline

“…From the perspective of their strong antioxidant and anti‐inflammatory capabilities, legume‐derived bioactive proteins appear to alleviate aging by clearing downstream or indirectly intermediate mitochondrial products. Interestingly, recent developments in antioxidants are nearing the provision of protection against mitochondrial oxidative damage (Luo et al., 2021). Due to barriers across complex mitochondrial membranes, cell‐penetrating peptides with mitochondrial targeting capabilities are effective tools for delivering exogenous therapeutic drugs to mitochondria (Xiao et al., 2021).…”

Melittin kills A549 cells by targeting mitochondria and blocking mitophagy flux

“…Consequently, mitochondria have emerged as an appealing target for therapeutic interventions in oncology. In recent years, there has been raising interest in the application of mitochondrial-targeted therapies in cancer treatment, including photodynamic therapy [ 18 ], drug delivery supplementation [ 19 , 20 ], as well as the development of mitochondria-targeted drugs [ 21 , 22 ] and related materials [ 23 ].…”