We present a new light cleavable polymer containing o-nitrobenzene thioacetal groups in the main chain. By conjugation to a PEG block, we synthesized block copolymers capable of forming nanoparticles in aqueous solution. We studied drug encapsulation and release using the model drug Nile Red. Irradiation with UV-A light (365 nm) leads to efficient degradation of the polymers and associated burst release of the payload. Unlike other thioacetal and thioketal polymers, these polymers are stable to reactive oxygen species (ROS), preventing non-triggered release. Moreover, the nanocarriers showed low cytotoxicity in cell viability experiments.

Polymeric micelles, due to their easy preparation and versatile properties, have been widely applied as one of the most popular carriers for chemotherapeutic agents. Such micelles primarily prevent the leakage of drugs during transportation and thus protect healthy tissue. Controlled drug release, which releases the drugs at the site of interest using internal or external stimuli as triggers, can further improve the safety of the drug delivery process. In this paper, we investigate whether ionizing radiation can be used to initiate release, focusing on using Cerenkov light as a possible trigger. For this purpose, micelles composed of the degradable polymer poly(ϵ-caprolactone-b-ethylene glycol) (PCL-PEO) were first loaded with the photosensitizer chlorin e6 (Ce6) and subsequently exposed to gamma or X-ray radiation of varying radiation doses. The results reveal that Ce6 was released from the micelles under radiation, regardless of the energy of incident photons, showing that Cerenkov light was not the driving force behind the observed release. SANS measurements showed that the volume fraction of the micelles containing Ce6 was reduced after exposure to radiation. This change in volume fraction suggests that the number of micelles was reduced, which was probably responsible for the release of Ce6. The exact mechanism, however, remains unclear. Subsequently, the PCL-PEO micelles were loaded with Ce6 and one of the following drugs: doxorubicin (Dox), docetaxel (DTX), and paclitaxel (PTX). Under radiation exposure, Dox, which is quite stable in single-loaded micelles, shows an enhanced release profile in the presence of Ce6, while DTX and PTX remained in the micelles, regardless of the presence of Ce6.