On demand, backbone-degradable polymers are attractive candidates of use in many biomedical, nanomaterials, and environmental applications.¹ Among the different applied stimuli, photo-mediated polymer degradation has been pursued in photo-patterning, polymer recycling and photo-triggered drug delivery, because of the high spatiotemporal tunability, as well as the noninvasive nature of light. Herein, novel photodegradable chemistries based on main-chain polyacetals, polythioacetals and polyacylhydrazones will be discussed. First, a dual degradable nanoparticulate drug delivery system that can be activated using visible light at very low doses delivered as unfocused pulse cues will be presented.^2,3 The polymeric drug carriers exhibited combinatorial photo- and chemo-degradation profiles, enabling the light controlled intracellular delivery of drug cocktails which allow for aggressive photoinduced cancer cell death. In the second part, a new class of photo-degradable thioacetal-based hydrogels, comprising PEG elastic chains and photo-sensitive cross-links, that undergo degradation upon exposure to UV light, will be discussed.⁴ The photodegradation mechanism was explored using kinetic studies of model small thioacetal molecules. The viscoelastic properties of the water swollen hydrogels during the photodegradation process and the reversible hydrogel formation upon heating were investigated by dynamic shear rheology for multiple photodegradation and reformation cycles restoring the initial mechanical properties of the hydrogel and thus revealing the re-processability of the system. Moreover, the ability of the hydrogels to encapsulate and release hydrophilic and hydrophobic model dye molecules upon photodegradation was studied. Finally, novel photo- and acid-degradable polymers based on hydrophilic polyacylhydrazones prepared via a polycondensation reaction of adipic acid dihydrazide with a dialdehyde poly(ethylene glycol) (PEG) macromonomer will be presented.⁵ An amphiphilic polyacylhydrazone-drug conjugate was synthesized by binding DOX, a hydrophobic anticancer drug, onto the polymer end-groups via acylhydrazone linkages and the polymer-drug conjugates were self-assembled into photodegradable spherical nanostructures in water. Irradiation of the self-assembled nanostructures resulted in the photolysis of the acylhydrazone bonds along the polymer chains, causing the degradation of the nanoparticles and the release of small molecules, PEG chains and the DOX drug. Finally, the synergistic effect of a low solution pH and light irradiation, on the disruption of the self-assembled prodrug nanostructures, due to the combined photo- and acido-lysis of the acylhydrazone bonds, was investigated. The release kinetics of the conjugated DOX molecules upon irradiation at pH 5.2 and 7.4, denoted that the release of the drug is dominated by the photoinduced cleavage of the acylhydrazone bonds, while a faster drug release rate of the therapeutic cargo was found at pH 2 reaching 82% free drug after 2 h irradiation time, due to the combined photolysis and acidolysis of the acylhydrazone bonds.

References:

1. T. Chen H. Wang, Y. Chu, C. Boyer, J. Liu, J. Xu, ChemPhotoChem 2019, 3, 1059; G. Pasparakis, et al. Macromol. Rapid Commun. 2012, 33, 183.
2. G. Pasparakis, Th. Manouras, A. Selimis, M. Vamvakaki and P. Argitis Angew. Chem. Int. Ed. 2011, 50, 4142-4145.
3. G. Pasparakis, Th. Manouras, M. Vamvakaki and P. Argitis Nat. Commun. 2014, 5, 3623.
4. M. Psarrou et al. 2023, submitted.
5. M. Psarrou, M. G. Kothri and M. Vamvakaki, Polymers 2021, 13, 2461.