Photoditazine-Loaded Polyelectrolyte Microcapsules for Differentiation-Enhanced Photodynamic Therapy of Neuroblastoma
Alexandra Yu. Sain1, Sofia A. Kreshchanovskaya1,2, Olga I. Efimova1, Vladimir P. Baklaushev3, Olga A. Sindeeva1; 1Skolkovo Institute of Science and Technology, Moscow, Russia; 2National Research University Higher School of Economics, Moscow, Russia; 3FSBI “Federal Center of Brain Research and Neurotechnologies”, Moscow, Russia
Abstract
Neuroblastoma is accounting for up to 10% of pediatric cancers. Despite advances in multimodal therapy, high-risk neuroblastoma remains associated with poor survival and substantial treatment-related toxicity. Here, we evaluated a dual-modality strategy combining differentiation induction with localized photodynamic therapy (PDT) using Photoditazine (PD)-loaded polyelectrolyte microcapsules in the N2A mouse neuroblastoma model.
N2A differentiation was induced using reduced-serum medium, retinoic acid (ATRA), brain-derived neurotrophic factor (BDNF), or ATRA+BDNF, with all protocols producing neuronal morphology; BDNF induced the most pronounced neurite outgrowth. PAH/PSS microcapsules with a mean diameter of 4.85 ± 0.52 μm were fabricated by a layer-by-layer approach. Empty microcapsules demonstrated high biocompatibility, maintaining N2A viability at 94.5 - 106.0% of untreated controls across 5 - 20 capsules/cell (all adjusted p > 0.75).
Free and encapsulated PD were subsequently evaluated at 2 - 8 μg/mL concentration range in both dark and light conditions. Free PD caused pronounced concentration-dependent dark toxicity in differentiated cells, reducing viability to 23 - 60% at 8 μg/mL depending on the differentiation protocol. In contrast, encapsulated PD maintained 83 - 111% viability under dark conditions across the tested concentrations, while preserving strong photodynamic activity after irradiation (660 nm, 20 J/cm2, 20 min), with viability reduced to 0 - 19%. Multifactorial analysis confirmed concentration and drug formulation as major determinants of cellular response.
These findings demonstrate that PD encapsulation can substantially reduce non-specific dark toxicity while preserving potent light-triggered cytotoxicity, supporting differentiation-coupled microcapsule delivery as a promising strategy for more selective neuroblastoma therapy.
Speaker
Alexandra Sain
Skolkovo Institute of Science and Technology
Russia
Discussion
Ask question
