Macrophage-mediated photodynamic therapy for renal cancer
Olga A. Sindeeva, 1, Aleksandra Sain, 1, Olga I. Gusliakova 1,2, Polina A. Demina 1,2, Gleb B. Sukhorukov, 1,3; 1Skolkovo Institute of Science and Technology, Moscow, Russia; 2Saratov State University, Saratov, Russia; 4National Research Ogarev Mordovia State University, Saransk, Russia; 3Life Improvement by Future Technologies Center, Moscow, Russia
Abstract
The development of novel, high-technology, and minimally invasive approaches for the treatment of kidney cancer remains a priority. This need is driven by the low sensitivity of kidney cancer to chemotherapy, the substantial adverse effects associated with targeted therapy and immunotherapy, and the early onset of metastasis, which results in a poor prognosis even after total nephrectomy. Using a mouse model of RenCa kidney cancer, tumor cells demonstrated high sensitivity to Photoditazine upon irradiation with a 660 nm laser. Photoditazine exhibited minimal dark toxicity. A bifunctional, cell-mediated therapeutic strategy was developed by combining the local delivery of autologous macrophages loaded with encapsulated Photoditazine and immunotherapy. This approach enables selective targeting of tumor cells through macrophage-mediated delivery of Photoditazine-containing carriers directly to the tumor site, followed by localized laser irradiation. The greatest therapeutic effect was observed in animals that additionally received interleukin-2. In contrast, no significant therapeutic effect was detected in the corresponding group without interleukin-2. These findings emphasize the importance of combination therapy and immunostimulation, particularly the activation of endogenous and tissue-resident macrophages. Histological analysis demonstrated that photodynamic therapy induced necrosis and edema in both healthy and tumor tissues of the renal cortex, especially following treatment with free Photoditazine. Encapsulation of Photoditazine and its delivery by autologous macrophages reduced damage to healthy tissue. In larger animal models and in clinical settings, this limitation could likely be further minimized through more precise laser targeting.
This work was supported by a grant from the Russian Science Foundation (RSF № 23-75-10070-П,
https://rscf.ru/project/23-75-10070-П/).
Speaker
Olga A. Sindeeva
Skolkovo Institute of Science and Technology
Russia
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