Enlightening release strategies: Accelerated nanoparticle degradation and substance release utilizing light- and pH-responsive polymers

Kramer, M.; van der Linde, M.; Hönscheid, L.; Horky, C.; Völlmecke, K.; Mulac, D.; Herrmann, F.; Kuckling, D.; Langer, K.

Zusammenfassung

To address the challenges associated with poor drug solubility and uncontrolled drug release in conventional dosage forms, a combination of polymer design and advanced drug delivery approaches has been employed. The development of pH-responsive nanoparticles for controlled and selective drug release represents a notable advance in adaptive nanomedicine. This study explores the design of a pH-responsive polymer, poly(1,4-phenyleneacetone dimethylene ketal) (PPADK). Additionally, the incorporation of light-responsive ortho-nitrobenzyl groups (o-NB-PPADK) enhanced the degradation upon exposure to light. Based on the polymer, nanoparticles were prepared using the solvent displacement method. The fluorescence dye Lumogen® Red was incorporated as a model substance. The nanoparticles were characterized by dynamic light scattering to determine their hydrodynamic diameter and size distribution, and the surface charge was analyzed. Atomic force microscopy was used to visualize the surface morphology. The nanoparticles remained stable under physiological pH conditions while exhibiting accelerated degradation and substance release in acidic environment, a property potentially exploitable for tumor targeting. Further enhanced degradation and correspondingly increased release was achieved by incorporating light-responsive elements in the polymer structure. The cytotoxicity of these newly designed nanoparticles was evaluated in cell culture using a breast cancer cell line. These results support the potential of o-NB-PPADK nanoparticles as a possible candidate for selective and effective cancer therapy, combining stimuli-responsive degradation mechanisms for improved therapeutic outcomes.