On-demand self-assembling peptide amphiphiles for cancer

Despite scientific progress, cancer still remains a challenge and therapies on the market present severe adverse effects which restrict applications and do not guarantee efficient treatments. Chemotherapeutics generally are highly toxic compounds with adverse effects on health, such as risk of damage to normal tissues or incomplete eradication of the cancer[1]. Doxorubicin (Dox)[2]is one of the most widely used and its long term application may cause dose dependent irreversible cardiomyopathy, liver damage and severe toxicity. Peptide drugs, in addition to having low toxicity, high specificity and ease of synthesis and modification, have the ability to develop self-assembling structures holding great promise for the development of functional nanomaterials. Here, we report the design, synthesis and characterization of selfassembled nanostructures, which integrate on their surface Dox and a cell penetrating peptide (gH625). gH625 was linked to a peptide segment of aliphatic residues (AAAAAAA) containing a lipidic tail (C19H38O2) attached to the ε-amino of a terminal lysine to generate a peptide amphiphile (gH625 PA). Dox was linked to the same lipidic tail through a labile linker (Dox PA). The self-assembly of the gH625 PA, Dox PA alone, or combined with coassembling shorter PA, was studied using spectroscopy and microscopy techniques. The designed PAs were shown to self-assemble. Our results provide insights into the design of an innovative concept of dynamic nanoplatforms, able to modulate their properties on demand, can be injectable and may be adapted to different cancers and also against other diseases.