The Assessment of the Combined Treatment of 5-ALA Mediated Photodynamic Therapy and Thalidomide on 4T1 Breast Carcinoma and 2H11 Endothelial Cell Line

Zduniak, Krzysztof; Gdesz-Birula, Katarzyna; Woźniak, Marta; Duś‐Szachniewicz, Kamila; Ziółkowski, Piotr

doi:10.3390/molecules25215184

Cited by 8 publications

(3 citation statements)

References 25 publications

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“…administered 50 mg kg −1 5-ALA (Day 1). The same or a similar dose is commonly used in small animal studies and induces PpIX accumulation in tumors after 3 h [ 34 , 53 , 54 ]. We intratumorally (i.t.)…”

Section: Evaluate Rdt With Cis@m-f and 5-ala In Solutionsmentioning

confidence: 99%

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

et al. 2022

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Background Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator–photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval. Methods Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells’ mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers. Results When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts. Conclusions Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation. Graphical Abstract

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Section: Evaluate Rdt With Cis@m-f and 5-ala In Solutionsmentioning

confidence: 99%

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

et al. 2022

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“…Several classes of molecules, such as tetrapyrrolic macrocycles and analogues, including porphyrins [64][65][66][67][68][69][70][71], phthalocyanines [72,73], chlorins [22,23,[74][75][76][77][78][79][80][81][82][83][84][85][86], the prodrug 5-aminolevulinic acid (5-ALA) [87][88][89] and other dyes, such as adequately conjugated indocyanine green [90][91][92][93][94], have been explored as PS in TNBC targeted therapy. Chlorins and their analogues are very interesting molecules; besides their natural source and/or semi-synthetic preparation, these molecules exhibit good absorption in the therapeutic window (600-800 nm), which is an important feature for a good candidate for clinical PDT, due to the better light penetration in tissues (≈1-2 cm), which overcomes the light penetration limitation when other photosensitizers are used, such as porphyrins [48,49,95].…”

Section: Targeted Therapy In Triple-negative Breast Cancermentioning

confidence: 99%

Current Photoactive Molecules for Targeted Therapy of Triple-Negative Breast Cancer

2021

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Cancer is the second leading cause of death worldwide; therefore, there is an urgent need to find safe and effective therapies. Triple-negative breast cancer (TNBC) is diagnosed in ca. 15–20% of BC and is extremely aggressive resulting in reduced survival rate, which is mainly due to the low therapeutic efficacy of available treatments. Photodynamic therapy (PDT) is an interesting therapeutic approach in the treatment of cancer; the photosensitizers with good absorption in the therapeutic window, combined with their specific targeting of cancer cells, have received particular interest. This review aims to revisit the latest developments on chlorin-based photoactive molecules for targeted therapy in TNBC. Photodynamic therapy, alone or combined with other therapies (such as chemotherapy or photothermal therapy), has potential to be a safe and a promising approach against TNBC.

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“…Additionally, a femtosecond NIR laser of was used in our research to induce hot electrons for generating ROS by the nonlinear two-photon effect, inducing less heat. Recently, the photodynamic therapy has been applied in the treatment of breast cancer, particularly on multidrug-resistant cancer cells [ 36 , 37 , 38 ]. Therefore, our aim is to study the feasibility of using GNPs as photosensitizer for the photodynamic therapy with two-photon lasers in the treatment of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Quasi-Spherical Gold Nanoparticles on Two-Photon Induced Reactive Oxygen Species for Cell Damage

2021

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The performance of quasi-spherical gold nanoparticles (GNPs) on the generation of reactive oxygen species (ROS) to cause cell damage, as irradiated by a two-photon laser, is studied. In this mechanism, hot electrons are generated from GNPs as irradiated by the two-photon laser, reacting with the molecules in the medium to produce ROS. We used laser scanning confocal microscopy with a low-fluence femtosecond Ti:Sapphire laser of 800 nm to observe the generated ROS in A431 cells, which were incubated with GNPs in advance. Subsequently, the cell morphology, cytoskeleton, and viability were investigated. In comparison with the control (no GNPs), the expression of ROS in these GNP-treated cells was enhanced after irradiation by the two-photon laser. Additionally, the disruption of cytoskeletons and the follow-up apoptosis of these GNP-treated cells are significantly increased as the number of laser shots increases. Moreover, we used N-acetyl-L-cysteine (NAC), an antioxidant, to inhibit the formation of ROS, to clarify whether the cytoskeletal disruption is caused by ROS rather than photothermal effects. Our results show that after two-photon irradiation, the ROS expression in these cells treated with GNPs plus NAC was significantly reduced. In addition, the cytoskeletal damage of these cells treated with GNPs and NAC was less than that of those treated with GNPs but without NAC; their cell viability after three days was almost the same with the control. These results illustrate that the induced ROS from the two-photon excited GNPs is the main cause of cell damage. The study may pave a way for the use of GNPs as a photosensitized therapeutic agent for two-photon photodynamic therapy on tumor treatment.

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The Assessment of the Combined Treatment of 5-ALA Mediated Photodynamic Therapy and Thalidomide on 4T1 Breast Carcinoma and 2H11 Endothelial Cell Line

Cited by 8 publications

References 25 publications

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

Current Photoactive Molecules for Targeted Therapy of Triple-Negative Breast Cancer

The Effect of Quasi-Spherical Gold Nanoparticles on Two-Photon Induced Reactive Oxygen Species for Cell Damage

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