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Photodynamic Therapy and Hyperthermia in Combination Treatment-Neglected Forces in the Fight against Cancer.

ABSTRACT: Cancer is one of the leading causes of death in humans. Despite the progress in cancer treatment, and an increase in the effectiveness of diagnostic methods, cancer is still highly lethal and very difficult to treat in many cases. Combination therapy, in the context of cancer treatment, seems to be a promising option that may allow minimizing treatment side effects and may have a significant impact on the cure. It may also increase the effectiveness of anti-cancer therapies. Moreover, combination treatment can significantly increase delivery of drugs to cancerous tissues. Photodynamic therapy and hyperthermia seem to be ideal examples that prove the effectiveness of combination therapy. These two kinds of therapy can kill cancer cells through different mechanisms and activate various signaling pathways. Both PDT and hyperthermia play significant roles in the perfusion of a tumor and the network of blood vessels wrapped around it. The main goal of combination therapy is to combine separate mechanisms of action that will make cancer cells more sensitive to a given therapeutic agent. Such an approach in treatment may contribute toward increasing its effectiveness, optimizing the cancer treatment process in the future.

SUBMITTER: Bienia A

PROVIDER: S-EPMC8399393 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Photodynamic Therapy and Hyperthermia in Combination Treatment-Neglected Forces in the Fight against Cancer.

Bienia Aleksandra A Wiecheć-Cudak Olga O Murzyn Aleksandra Anna AA Krzykawska-Serda Martyna M

Pharmaceutics 20210727 8

Cancer is one of the leading causes of death in humans. Despite the progress in cancer treatment, and an increase in the effectiveness of diagnostic methods, cancer is still highly lethal and very difficult to treat in many cases. Combination therapy, in the context of cancer treatment, seems to be a promising option that may allow minimizing treatment side effects and may have a significant impact on the cure. It may also increase the effectiveness of anti-cancer therapies. Moreover, combinatio ...[more]

PMID: 34452108

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Project description:Innovative synthesis routes revolutionized nanomaterial combination and design possibilities resulting in a new generation of fine-tuned nanoparticles featuring exquisite shape and constitution control. However, there is still room for improvement when it comes to the development of multi-functional nanoparticle agents merging a plurality of therapeutic functions to tackle tumors simultaneously by synergic mechanisms. Herein, we report the design of an optimized nanohybrid for cancer tri-therapy featuring a maghemite (γ-Fe2O3) nanoflower-like multicore nanoparticle conceived for efficient magnetic hyperthermia (MHT) and a spiky copper sulfide shell (IONF@CuS) with a high near-infrared (NIR) absorption coefficient suitable for photothermal (PTT) and photodynamic therapy (PDT). Methods: Spiky-like IONF@CuS nanohybrids were obtained through a straightforward and scalable water-based template sacrificial synthesis, which allows the shell shape control by tuning polyvinylpyrrolidone (PVP) concentration. A comprehensive characterization of nanohybrid size, shape and structural properties was carried out by combining complementary TEM, SEM, HR-TEM, EELS, XRD and NTA. The all-in-one therapeutic multi-functionality was assessed on cancer cells and on tumor-bearing nude mice. Results: Tests carried out on IONF@CuS nanohybrid aqueous dispersion demonstrated their impressive efficiency to convert light (conversion coefficient = 42 ± 6 %) and magnetic stimulation (SAR ~ 350 W g-1) into heat as well as to induce concurrent reactive oxygen species (ROS) formation upon laser irradiation. Such capabilities were further confirmed in cellular environment by in vitro tests and at the organism level by in vivo tests in a murine tumor model. Notably, complete tumor regression was obtained for the PTT mode at low Cu concentration. Overall, these results allowed determining windows of applicability for each therapy individually or in combination. Conclusions: Altogether, the obtained data evidence the successful synthesis of a unique tri-therapeutic nanoparticle featuring highly relevant assets for clinical translation such as reduced nanoparticle administered dose, reduced laser power exposure, reduced magnetic field frequency, and the possibility of serial heating cycles and therapy monitoring by photoacoustic (PA) and magnetic resonance imaging (MRI). Furthermore, the integration of the dual heating capability (MHT + PTT) with the PDT insult offers a unique asset to tackle tumors by multiple cytotoxic strategies in order to improve the therapeutic outcome in a broader spectrum of clinical conditions.

Project description:Thermal inactivation of glyceraldehyde-3-phosphate dehydrogenase appeared to be caused by a conformational mechanism, without involvement of covalent reactions. On the other hand, photodynamic inactivation of the enzyme (induced by illumination in the presence of Photofrin II) was caused by photo-oxidation of the essential thiol group in the active centre. A short photodynamic treatment of the enzyme, leading to only a limited inactivation, caused a pronounced potentiation of subsequent thermal inactivation, as measured over the temperature range 40-50 degrees C. Analysis of the experimental results according to the Arrhenius equation revealed that both the activation energy of thermal inactivation and the frequency factor (the proportionality constant) were significantly decreased by the preceding photodynamic treatment. The experimental results indicate a mechanism in which limited photodynamic treatment induced a conformational change of the protein molecule. This conformational change did not contribute to photodynamic enzyme inhibition, but was responsible for the decreased frequency factor and activation energy of subsequent thermal inactivation of the enzyme. The opposing effects of decreased activation energy and decreased frequency factor resulted in potentiation of thermal inactivation of the enzyme over the temperature range 40-50 degrees C. With other proteins, different results were obtained. With amylase the combined photodynamic and thermal effects were not synergistic, but additive, and photodynamic treatment had no effect on the frequency factor and the activation energy of thermal inactivation. With respect to myoglobin denaturation, the photodynamic and thermal effects were antagonistic over the whole practically applicable temperature range. Limited photodynamic treatment protected the protein against heat-induced precipitation, concomitantly increasing both the frequency factor and the activation energy of the process. These results offer a model for one of the possible mechanisms of synergistic interaction between photodynamic therapy and hyperthermia in cancer treatment.

Dataset Information

Photodynamic Therapy and Hyperthermia in Combination Treatment-Neglected Forces in the Fight against Cancer.

Publications

Photodynamic Therapy and Hyperthermia in Combination Treatment-Neglected Forces in the Fight against Cancer.

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