Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen‐Dependent Photodynamic Cancer Therapy

Abstract

Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene‐derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light‐sensitive molecule is not a mediator but is itself the cytotoxic agent. As a derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic exists in two thermally stable photoforms that are interconvertible by light of different wavelengths. The isomer generated by visible light shows much stronger toxicity against tumor cells than the UV‐generated isomer. First in vivo applications are demonstrated on a tumor animal model to illustrate how the peptidomimetic can be administered in the less toxic form and then activated locally in a solid tumor by visible light.

Molecular photoswitches in aqueous environments

“…However, this derivative was one of the most hydrophobic ones and was poorly water-soluble, forming aggregates in aqueous solutions. 698,700 The second analogue, the gramicidin S derivative 4.53 could be further tested on an animal tumor model 701 to successfully target cancer cells in its more cytotoxic open form, while the closed form was 5.5 to 8-fold less active. In contrast to the parent compound, 4.53 was stable in blood and resistant to proteolysis in vivo.…”

Recent Implementations of Molecular Photoswitches into Smart Materials and Biological Systems

“…Although DAE photoisomerization does not induce large geometry changes, a significant difference in cytotoxicity has been observed upon photoisomerization of a DAE‐containing analogue of a cyclic peptide, gramicidin S, presumably due to meaningful changes in backbone flexibility . This compound has been successfully applied to a tumor animal model as an alternative to oxygen‐dependent photodynamic anticancer therapy …”

Reversible Photochemical Switching via Plasmonically Enhanced Upconversion Photoluminescence

“…Combined with improved optical performance, this facile fabrication methodology for largescale production of a fastresponse photoisomerization system provides an innova tive alternative for various feasible applications, such as optically switchable electronic devices, enzyme/inhibitor mimicking, and standard methods of superresolution PL imaging. [2,[29][30][31][32][33][34][35]…”