Engineering of light responsive Elastin-Like Polypeptides nanoplatforms for chemo- and photodynamic anticancer therapies

Elastin-Like Peptides (ELPs) are biopolymers characterized by the repeating sequence (GXGVP)n (with X any amino acid except proline) derived from the hydrophobic domain of human tropoelastin. They have attracted significant interest for applications in drug delivery and tissue engineering because of their biocompatibility, biodegradability and non-immunogenicity. ELPs exhibit a reversible phase separation whereby samples remain soluble below a transition temperature (Tt) but form amorphous coacervates above Tt. This property can be used to co-assembly different functionalized polypeptides into nanoparticles by mixing them together and heating with a critical heating rate. In the present study, we explored different nanoplatforms based upon light responsive ELPs that combine chemo and photodynamic therapies for anticancer smart nanomedicine. A photosensitizer and/or a drug were conjugated to an hydrophobic methionine-containing monoblock ELP that got co-assembled into nanoparticles together with a diblock ELP. To deliver the cargo to the tumor tissue, the nanoparticles were targeted to selectively bind tumor cells. Light irradiation causes the generation of singlet oxygen that, aside from causing direct damage to cells, facilitates the disassembly of the particles oxidizing the methionine residue into a hydrophilic sulfoxide derivative and enhancing in this way the penetration into the tumor tissue. The drug (MMAE) is linked to the monoblock ELP via a lysosomally cleavable dipeptide that allows its release once the nanoparticles are bound to cells. These innovative platforms offer promising results, showing a surprisingly high efficacy of the chemo-photodynamic dual therapy compared to the single therapies.