Transformable Helical Self-Assembly for Cancerous Golgi Apparatus Disruption

Abstract

Golgi apparatus is a major subcellular organelle responsible for drug resistance. Golgi apparatus-targeted nanomechanical disruption provides an attractive approach for killing cancer cells by multimodal mechanism and avoiding drug resistance. Inspired by the poisonous twisted fibrils in Alzheimer's brain tissue and enhanced rigidity of helical structure in nature, we designed transformable peptide C 6 RVRRF 4 KY that can selfassemble into nontoxic nanoparticles in aqueous medium but transformed into left-handed helical fibrils (L-HFs) after targeting and furin cleavage in the Golgi apparatus of cancer cells. The L-HFs can mechanically disrupt the Golgi apparatus membrane, resulting in inhibition of cytokine secretion, collapse of the cellular structure, and eventually death of cancer cells. Repeated stimulation of the cancers by the precursors causes no acquired drug resistance, showing that mechanical disruption of subcellular organelle is an excellent strategy for cancer therapy without drug resistance. This nanomechanical disruption concept should also be applicable to multidrug-resistant bacteria and viruses.

Bioactive Peptide Nano-assemblies with pH-Triggered Shape Transformation for Antibacterial Therapy

“…Toward this direction, supramolecular self-assembly of short peptide subunits has gained immense attention as a bottom-up methodology to fabricate several materials at the nano dimension . Novel nanostructures can be developed by harnessing the advantages of dynamic self-assembly and adaptability of peptide-based biomolecules. , Furthermore, peptide/protein-based self-assembled systems have been used widely in developing antimicrobial agents because of their structural versatility and functional benefits. ,− Several peptides were found to exhibit stimuli-responsive assembly behavior, and their ability to achieve diverse nanoscale structures was reported to be highly dependent on the surrounding environmental conditions. , Such intrinsic transmorphic properties of peptide nanostructures facilitate the development of stimuli-responsive nanomaterials displaying efficient antimicrobial properties. − Hence, the emerging paradigm has witnessed a shift toward constructing an array of well-defined versatile nanostructures with diverse antimicrobial functions and several other biomedical applications. − …”

An AIEgen-based “turn-on” probe for sensing cancer cells and tiny tumors with high furin expression

“…apparatus. 22,43 Similarly, the fluorescence of PGA-BFA-treated 4T1 also showed good co-localization with the Golgi-Tracker at 6 h (Fig. 5g) with a Pearson's correlation coefficient of 0.55 (Fig.…”

“…20 Also, furin plays an important role in tumor development, such as cleaving matrix metalloproteinases 14 to promote tumor migration, 21 and has become a popular target for imaging 18 and treating tumors. 22 The Liang group reported a dual-enhanced tetraphenylethene (TPE) probe for sensing furin at the cellular level. 23 Xia and his collaborators used lifetime criteria to improve the accuracy of the AIE probe for the identification of cell types with different furin expression levels.…”

Self-Amplifying Assembly of Peptides in Macrophages for Enhanced Inflammatory Treatment

“…Controllable self-assembly of peptides in living cells via either external or internal stimuli allows for creation of peptide nanostructures with the broad functions ranging from disease diagnosis to treatment. − Among the applicable stimuli, enzymes have been considered as one of versatile strategies to regulate the self-assembly of peptides due to their reliable selectivity in the catalysis of chemical reactions. − In this context, several enzymes have been utilized in manipulating peptide self-assembly in living cells, including alkaline phosphatase, nitroreductase, caspase-3/7, among others. − However, in most cases, expression of the utilized enzymes is only naturally occurring, and there is a lack of intimate association between the expression of enzymes and the self-assembly of peptides. Hence, precisely manipulating the assembly of peptides in specific cells significantly depends on the overexpression of enzymes, thus leading to the limitation of enzymes to the aforementioned categories and particularly for the challenges in the detection of pathological cells at the early stage and interference of their fate.…”