Abstract

Photodynamic therapy (PDT) is a minimally invasive treatment that utilizes photosensitizing agents activated by specific light wavelengths to produce reactive oxygen species, leading to the destruction of targeted cells. However, the efficacy of these photosensitizers is compromised by their limited solubility and stability. Although nanocarriers for photosensitizers such as boron nitride nanotubes (BNNTs) have been investigated for their biocompatibility and stability, their tendency to form large aggregates in aqueous solutions poses a challenge. In this study, a hydrogel based on dialdehyde starch and chitosan with dynamic Schiff-type bonds is presented as a carrier for hybrid polythiophene/boron nitride nanotube-based photosensitizers to target and destroy cancer cells. The BNNTs were non-covalently functionalized with polythiophenes (PT-BNNTs), having different functional groups on the side chains. The obtained water-soluble PT-BNNT hybrids exhibit a red-shift in their absorption spectra, aligning with the optimal therapeutic window (600 nm to 900 nm) for PDT. The hydrogels with PT-BNNTs showed rapid gelation (<1 min) and remarkable self-healing behavior within 20 min, as confirmed by rheological measurements, owing to the imine bonds. In vitro assays with DU-145 cancer cells showed that hydrogels containing PT-BNNTs significantly increased reactive oxygen species production, by up to 4.6 times compared to hydrogels without PT-BNNTs. Furthermore, cell viability decreased by 70 % after irradiation compared to controls with non-irradiated hydrogels. These results indicate that self-healing chitosan/dialdehyde starch hydrogels with polythiophene-functionalized BNNTs have great potential as photosensitizer carriers for photodynamic cancer therapy. © 2025