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Keywords = X-ray photodynamic therapy

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17 pages, 1950 KB  
Article
Talaporfin Sodium as a Clinically Translatable Radiosensitizer in Radiodynamic Therapy
by Junko Takahashi, Junkoh Yamamoto, Kohei Suzuki, Shohei Nagasaka, Kaizhen Yang, Haobo Zhao and Teppei Yamaoka
Biomolecules 2025, 15(12), 1748; https://doi.org/10.3390/biom15121748 - 18 Dec 2025
Viewed by 418
Abstract
Talaporfin sodium (mono-L-aspartyl chlorin e6; NPe6), a second-generation photosensitizer, is clinically used in photodynamic therapy (PDT). It accumulates preferentially in tumors and exhibits deep tissue penetration, rapid systemic clearance, and minimal photosensitivity. However, treatment of deep-seated malignancies remains challenging. Here, we demonstrate that [...] Read more.
Talaporfin sodium (mono-L-aspartyl chlorin e6; NPe6), a second-generation photosensitizer, is clinically used in photodynamic therapy (PDT). It accumulates preferentially in tumors and exhibits deep tissue penetration, rapid systemic clearance, and minimal photosensitivity. However, treatment of deep-seated malignancies remains challenging. Here, we demonstrate that talaporfin sodium undergoes physicochemical reactions with X-rays to generate reactive oxygen species, a mechanism analogous to that of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX in radiodynamic therapy (RDT). To evaluate its therapeutic efficacy, we employed a pancreatic cancer xenograft model using MIA PaCa-2 cells in mice. Talaporfin sodium was administered intravenously 2 h before X-ray exposure, followed by fractionated X-ray irradiation (3 Gy daily for 3 consecutive days). Talaporfin-mediated RDT significantly inhibited tumor growth compared with radiation therapy alone. Furthermore, an exploratory RNA-seq analysis of xenografts revealed transcriptional signatures of stress and immune activation, suggesting that talaporfin-mediated RDT enhances oxidative and immunogenic responses within the tumor microenvironment. These findings highlight the potential of talaporfin sodium as a clinically translatable radiosensitizer for RDT, offering a promising strategy for the treatment of deep-seated cancers such as pancreatic carcinoma. Full article
(This article belongs to the Section Chemical Biology)
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18 pages, 5447 KB  
Article
Development and Application of Visible-Light-Responsive Perylene Diimide Functionalized Silk Fibroin/Polylactic Acid Antibacterial Nanofibrous Membranes
by Sheng Lv, Hongyu Lin, Ying Lin, Qingyan Peng, Yuyang Song, Xiaodong Tan, Xiao Yang and Shixiong Yi
Int. J. Mol. Sci. 2025, 26(23), 11533; https://doi.org/10.3390/ijms262311533 - 28 Nov 2025
Viewed by 422
Abstract
The issue of antibiotic resistance is becoming increasingly severe, urgently requiring the development of new antibacterial strategies. Photodynamic therapy (PDT) has gradually emerged as a promising alternative due to its spatiotemporal controllability, low risk of drug resistance, and broad-spectrum antibacterial properties. However, most [...] Read more.
The issue of antibiotic resistance is becoming increasingly severe, urgently requiring the development of new antibacterial strategies. Photodynamic therapy (PDT) has gradually emerged as a promising alternative due to its spatiotemporal controllability, low risk of drug resistance, and broad-spectrum antibacterial properties. However, most existing photosensitizers (PSs) are hydrophobic, which limits their application efficiency in PDT. To address this problem, we designed and synthesized a water-soluble perylene diimide derivative (PDICN-CBn) as a photosensitizer. By introducing quaternary ammonium salt groups, its water solubility was improved, and antibacterial activity was enhanced. Subsequently, PDICN-CBn was assembled into silk fibroin/polylactic acid (SF/PLA) nanofibrous membranes via electrospinning technology, successfully constructing a visible-light-responsive ternary composite nanofibrous membrane (SF/PLA@PDICN-CBn). Using various characterization methods such as nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM), the microstructure, chemical composition, and structural characteristics of the nanofibrous membranes were systematically analyzed, verifying the successful synthesis of the photosensitizer and its assembly into the nanofibrous membranes. In the reactive oxygen species (ROS) experiment, electron spin resonance (ESR) spectra showed that PDICN-CBn efficiently generated singlet oxygen (1O2), superoxide anion (·O2), and hydroxyl radical (·OH) under visible light irradiation, confirming its ability to produce different types of ROS through both type I and type II photodynamic reactions. In the antibacterial experiments, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and methicillin-resistant Staphylococcus aureus (MRSA) were selected for a series of tests, including plate-counting antibacterial assays, bacterial live/dead staining, and SEM observation of morphology. The results showed that 8 μg/mL of PDICN-CBn effectively destroyed the bacterial cell membrane structure and killed bacteria (bactericidal rate > 95%) after 2 h of visible light irradiation. This work successfully developed a novel visible-light-responsive SF/PLA@PDICN-CBn nanofibrous membrane with a dual antibacterial system combining photodynamic and electrostatic adsorption antibacterial properties, providing new ideas and methods for the design and development of photodynamic antibacterial materials. The prepared nanofibrous membrane has potential application values in fields such as wound dressings and medical protective materials and is expected to provide strong support for solving clinical infection problems. Full article
(This article belongs to the Special Issue Biomaterials and Antibacterial Materials for Medical Applications)
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16 pages, 2794 KB  
Article
Construction and Activity of Cisplatin-Loaded Chitosan–Zinc Amino-Porphyrin Photosensitizer Hydrogel
by Hongmei Zhang, Dongqing Li, Pengge Wang, Yunxia Yang, Daliang Zhu and Yanqing Wang
Gels 2025, 11(12), 948; https://doi.org/10.3390/gels11120948 - 26 Nov 2025
Viewed by 387
Abstract
Cisplatin resistance remains a major impediment to the successful chemotherapy of various solid tumors, including ovarian, lung, and head and neck cancers. Diverse drug delivery systems with photodynamic specificity significantly target diseased cells precisely. Herein, a homogeneous photodynamic hydrogel drug-loading network based on [...] Read more.
Cisplatin resistance remains a major impediment to the successful chemotherapy of various solid tumors, including ovarian, lung, and head and neck cancers. Diverse drug delivery systems with photodynamic specificity significantly target diseased cells precisely. Herein, a homogeneous photodynamic hydrogel drug-loading network based on chitosan (CS) containing zinc amino-porphyrin (ZnTAPP) has been developed for carrying cisplatin (CDDP). Aldehyde groups of glutaraldehyde acted as a bridge to connect ZnTAPP and CS. CDDP was then loaded in CS-ZnTAPP hydrogel to construct the anticancer drug system synergistically. Multiple analysis methods were applied to evaluate the chemical structure and physical properties of hydrogels, including a Fourier transform infrared spectrometer, scanning electron microscopy, an X-ray powder diffractometer, rheological measurements, etc. CS-ZnTAPP hydrogels as well as CS-ZnTAPP-CDDP hydrogels, generated abundant singlet oxygen rapidly for photodynamic therapy. Finally, the hydrogels exhibited significant anticancer activities under irradiation; the IC50 was reduced to 10.936 μg/mL toward CDDP-resistant lung cancer cells (A549/CDDP). The new hydrogel could be applied as a photodynamic anticancer drug delivery system to overcome cisplatin resistance. Full article
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16 pages, 3415 KB  
Article
Poly(glycerol)-Functionalized Gadolinium Tungstate Nanoflakes Loaded with Chlorin e6: Photodynamic Efficacy and Radiosensitization Potential for Multimodal Cancer Therapy
by Heon Gyu Kang and Lukas R. H. Gerken
Materials 2025, 18(22), 5198; https://doi.org/10.3390/ma18225198 - 16 Nov 2025
Viewed by 610
Abstract
Gadolinium (Gd)-based nanomaterials have attracted a considerable amount of attention in cancer treatment research due to their applicability in radiotherapy. However, the clinical translation of Gd-based nanomaterials is limited by their high density and poor dispersibility in aqueous media, thereby necessitating surface functionalization [...] Read more.
Gadolinium (Gd)-based nanomaterials have attracted a considerable amount of attention in cancer treatment research due to their applicability in radiotherapy. However, the clinical translation of Gd-based nanomaterials is limited by their high density and poor dispersibility in aqueous media, thereby necessitating surface functionalization with biocompatible polymers. In this study, gadolinium tungstate (Gd2(WO4)3) nanoflakes (GW Nfs) were functionalized with poly(glycerol) (PG) to enhance their dispersibility and stability in aqueous media. Due to their high-Z elemental composition, the GW Nfs generated reactive oxygen species (ROS) under X-ray irradiation, with improved dispersibility induced by PG functionalization further enhancing ROS productivity compared to GW Nfs. Furthermore, PG-GW loaded with the photosensitizer chlorin e6 (Ce6) demonstrated strong photocytotoxicity at Ce6 concentrations as low as 0.2 μg mL−1 under light irradiation. Taken together, these results demonstrate that PG-GW/Ce6 is a promising nanomaterial for photodynamic therapy while also offering prospects for bimodal photon cancer therapy with X-rays. Full article
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17 pages, 2674 KB  
Article
Preparation and Performance of Phthalocyanine @ Copper Iodide Cluster Nanoparticles for X-Ray-Induced Photodynamic Therapy
by Wei Xie, Yunan Li, Guoyan Tang, Zhihua Li, Mengyu Yao, Biyuan Zheng, Xingshu Li and Jian-Dong Huang
Molecules 2025, 30(21), 4229; https://doi.org/10.3390/molecules30214229 - 29 Oct 2025
Viewed by 934
Abstract
The efficacy of X-ray-induced photodynamic therapy (X-PDT) for deep tumors is often hindered by conventional scintillators, typically rare-earth nanoparticles plagued by long-term toxicity and suboptimal scintillation yields. Here, we introduce a copper iodide (Cu-I) cluster, Cu2I2(PPh3)2 [...] Read more.
The efficacy of X-ray-induced photodynamic therapy (X-PDT) for deep tumors is often hindered by conventional scintillators, typically rare-earth nanoparticles plagued by long-term toxicity and suboptimal scintillation yields. Here, we introduce a copper iodide (Cu-I) cluster, Cu2I2(PPh3)2(pz), composed of earth-abundant elements, as an efficient and biocompatible energy transducer for X-PDT. A theranostic nanoplatform, CuI@PcNP, was engineered by co-encapsulating the Cu-I cluster and a phthalocyanine photosensitizer (Pc4OH) within a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2K) matrix, which confers excellent physiological stability. This nano-architecture ensures nanoscale proximity between the cluster (donor) and photosensitizer (acceptor), facilitating efficient (58%) Förster resonance energy transfer (FRET) while overcoming aggregation-induced quenching. Upon X-ray irradiation, the platform effectively converted X-rays to visible light, activating Pc4OH to generate potent reactive oxygen species (ROS) and inducing significant dose-dependent cytotoxicity in human hepatocellular carcinoma (HepG2) cells. In a murine hepatoma model, enabling image-guided X-PDT that resulted in a 77.4% tumor inhibition rate with negligible systemic toxicity. Collectively, this work pioneers the integration of phthalocyanine with Cu-I clusters, providing a stable and versatile nanoplatform for image-guided X-PDT. Full article
(This article belongs to the Special Issue Photochemistry in Asia)
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27 pages, 5224 KB  
Article
Cellulose-Derived Gels for Topical Delivery: HPMC as a Functional Matrix for Porphyrinic Photosensitizers
by Emma Adriana Ozon, Andreea Mihaela Burloiu, Adina Magdalena Musuc, Gina Manda, Valentina Anuta, Cristina Elena Dinu-Pîrvu, Dumitru Lupuliasa, Ionela Victoria Neagoe, Mihai Anastasescu, Radu Petre Socoteanu, Irina Atkinson, Raul-Augustin Mitran, Daniela C. Culita and Rica Boscencu
Gels 2025, 11(10), 824; https://doi.org/10.3390/gels11100824 - 14 Oct 2025
Cited by 1 | Viewed by 1873
Abstract
Hydroxypropyl methylcellulose (HPMC) is a biocompatible polymer widely used in topical formulations due to its suitable rheological behavior, film-forming capacity, and good compatibility with different active pharmaceutical ingredients. The present study demonstrates the potential of HPMC-based gels for dermal delivery of porphyrinic photosensitizers, [...] Read more.
Hydroxypropyl methylcellulose (HPMC) is a biocompatible polymer widely used in topical formulations due to its suitable rheological behavior, film-forming capacity, and good compatibility with different active pharmaceutical ingredients. The present study demonstrates the potential of HPMC-based gels for dermal delivery of porphyrinic photosensitizers, aiming to enhance the efficiency of photodynamic therapy (PDT) in potential skin cancer applications. HPMC-based gel incorporating two previously synthesized porphyrinic photosensitizers, named 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), was developed and carefully characterized regarding its rheological behavior, texture, and in vitro activity. Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), atomic force microscopy (AFM), fluorescence, and UV-Vis spectroscopy were carried out to evaluate the structural and morphological changes induced by the incorporation of the porphyrins in the HPMC gel matrix. The gels were subsequently evaluated by pharmacotechnical analysis, including pH (7.2 for both HPMC-P2.1 and HPMC-P2.2), viscosity, spreadability, texture profile analysis, and drug content uniformity. Rheological behavior confirmed the pseudoplastic behavior, suggesting a structured system with a gel-like consistency, while physical measurements demonstrated the stability and preserved functionality of the photosensitizers within the HPMC matrix. In vitro studies revealed an efficient cellular internalization of selected porphyrins into human epidermoid carcinoma cells, a critical requirement for topical PDT applications. The study highlights the capability of HPMC gels to serve as effective delivery platforms for porphyrin-based photosensitizers, supporting their application in localized skin cancer treatment through PDT. Full article
(This article belongs to the Special Issue Hydrogel for Sustained Delivery of Therapeutic Agents (3rd Edition))
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25 pages, 2500 KB  
Article
Green Synthesis of Gold Nanoparticles Using Mandragora autumnalis: Characterization and Evaluation of Its Antioxidant and Anticancer Bioactivities
by Ghosoon Albahri, Adnan Badran, Heba Hellany, Nadine Kafrouny, Riham El Kurdi, Mohamad Alame, Akram Hijazi, Marc Maresca, Digambara Patra and Elias Baydoun
Pharmaceuticals 2025, 18(9), 1294; https://doi.org/10.3390/ph18091294 - 29 Aug 2025
Cited by 1 | Viewed by 1336
Abstract
Background: One of the most widely used metal nanoparticles in biological applications is gold, which has unique physicochemical characteristics. Strong localized surface plasmon resonance (LSPR) endows them with exceptional optical properties that facilitate the development of innovative methods for biosensing, bioimaging, and [...] Read more.
Background: One of the most widely used metal nanoparticles in biological applications is gold, which has unique physicochemical characteristics. Strong localized surface plasmon resonance (LSPR) endows them with exceptional optical properties that facilitate the development of innovative methods for biosensing, bioimaging, and cancer research, particularly in the context of photothermal and photodynamic therapy. Methods: This study marked the first time that Mandragora autumnalis ethanolic extract (MAE) was utilized in the environmentally friendly synthesis of gold nanoparticles (AuNPs). Several characterization methods, including dynamic light scattering analysis (DLS), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and biological methods, were used to emphasize the anti-cancerous activity of the biogenic AuNPs. Results: MAE-AuNPs showed a surface plasmon resonance band at 570 nm. DLS and SEM demonstrated the synthesis of small, spherical AuNPs with a zeta potential of −19.07 mV. The crystalline nature of the AuNPs was confirmed by the XRD pattern, and data from FTIR and TGA verified that MAE-AuNPs played a part in stabilizing and capping the produced AuNPs. In addition, the MAE-AuNPs demonstrated their potential effectiveness as antioxidant and anticancer therapeutic agents by demonstrating radical scavenging activity and anticancer activity against a number of human cancer cell lines, specifically triple-negative breast cancer cells. Conclusions: Green synthesis techniques are superior to other synthesis methods because they are simple, economical, energy-efficient, and biocompatible, which reduces the need for hazardous chemicals in the reduction process. This article highlights the significance of characterizing MAE-AuNPs and evaluating their antioxidant and anticancer properties. Full article
(This article belongs to the Special Issue Pharmacologically Active Compounds from Plants)
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23 pages, 5631 KB  
Article
Obtention and Characterization of TiO2-Folic Acid-ZnPc Semiconductor Nanoparticles for Photodynamic Therapy Against Glioma Cells
by Citlali Ekaterina Rodríguez-Pérez, Sonia Rodríguez-García, Ma. Elena Manríquez-Ramírez, A. Martin Ortiz-Torres, Francisco Tzompantzi-Morales and Emma Ortiz-Islas
Pharmaceutics 2025, 17(8), 1071; https://doi.org/10.3390/pharmaceutics17081071 - 19 Aug 2025
Viewed by 1144
Abstract
Background/Objectives: This study reports the synthesis of TiO2 nanoparticles, their functionalization with folic acid (FA), and the subsequent loading with zinc phthalocyanine (ZnPc) to develop photosensitizers for photodynamic therapy (PDT) targeting glioma cells. Methods: TiO2, TiO2-FA, and TiO [...] Read more.
Background/Objectives: This study reports the synthesis of TiO2 nanoparticles, their functionalization with folic acid (FA), and the subsequent loading with zinc phthalocyanine (ZnPc) to develop photosensitizers for photodynamic therapy (PDT) targeting glioma cells. Methods: TiO2, TiO2-FA, and TiO2-FA-ZnPc nanoparticles were synthesized via a sol–gel process involving the hydrolysis and condensation of titanium (IV) isopropoxide. FA and ZnPc were incorporated in vitro during the synthesis. The resulting materials were characterized by transmission and scanning electron microscopy (TEM and SEM), X-ray diffraction (XRD), Raman and UV–Vis spectroscopy, thermogravimetric analysis (TGA), and nitrogen adsorption–desorption measurements. Reactive oxygen species (ROS) generation was evaluated in vitro using the 1,3-diphenylisobenzofuran (DPBF) probe. A 40 ppm solution of each TiO2 system was irradiated with UV light, and the degradation of DPBF was monitored. Biological assays were conducted to assess the viability of human glioblastoma cells (LN18 and U251) incubated with the TiO2-based materials, with and without UV exposure. Human fibroblast cells (BJ) were used to evaluate biocompatibility. Results: All TiO2-based materials retained key characteristics, including high surface area (~600–700 m2/g), mesoporous structure (pore diameter ~4–5 nm), mixed anatase–amorphous morphology, and a bandgap of approximately 3.46 eV. The UV–Vis spectrum of TiO2-FA-ZnPc displayed additional absorption bands in the visible region (600–700 nm), consistent with ZnPc incorporation. Upon UV irradiation, the DPBF absorbance at 410 nm decreased over time, indicating ROS generation and resulting in complete degradation within 10 min (TiO2), 12 min (TiO2-FA), and 14 min (TiO2-FA-ZnPc). BJ cells exhibited good biocompatibility at all concentrations. LN18 and U251 cells showed no cytotoxicity below 100 μg/mL unless exposed to UV light. Conclusions: The synthesized TiO2-based systems demonstrate good biocompatibility and significant phototoxicity under UV irradiation, highlighting their strong potential for application in photodynamic therapy. Full article
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30 pages, 20069 KB  
Article
Evaluation of CoFe2O4-L-Au (L: Citrate, Glycine) as Superparamagnetic–Plasmonic Nanocomposites for Enhanced Cytotoxic Activity Towards Oncogenic (A549) Cells
by Alberto Lozano-López, Mario E. Cano-González, J. Ventura-Juárez, Martín H. Muñoz-Ortega, Israel Betancourt, Juan Antonio Zapien and Iliana E. Medina-Ramirez
Int. J. Mol. Sci. 2025, 26(16), 7732; https://doi.org/10.3390/ijms26167732 - 10 Aug 2025
Cited by 1 | Viewed by 1073
Abstract
We investigated the influence of gold deposition on the magnetic behavior, biocompatibility, and bioactivity of CoFe2O4 (MCF) nanomaterials (NMs) functionalized with sodium citrate (Cit) or glycine (Gly). The resulting multifunctional plasmonic nanostructured materials (MCF-Au-L, where L is Cit, Gly) exhibit [...] Read more.
We investigated the influence of gold deposition on the magnetic behavior, biocompatibility, and bioactivity of CoFe2O4 (MCF) nanomaterials (NMs) functionalized with sodium citrate (Cit) or glycine (Gly). The resulting multifunctional plasmonic nanostructured materials (MCF-Au-L, where L is Cit, Gly) exhibit superparamagnetic behavior with magnetic saturation of 59 emu/g, 55 emu/g, and 60 emu/g, and blocking temperatures of 259 K, 311 K, and 322 K for pristine MCF, MCF-Au-Gly, and MCF-Au-Cit, respectively. The MCF NMs exhibit a small uniform size (with a mean size of 7.1 nm) and an atomic ratio of Fe:Co (2:1). The gold nanoparticles (AuNPs) show high heterogeneity as determined by high-resolution transmission electron microscopy (HR-TEM) and energy-dispersive X-ray spectroscopy (EDX). The UV-Vis spectroscopy of the composites reveals two localized surface plasmons (LSPs) at 530 nm and 705 nm, while Fourier Transformed-Infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) confirm the presence of Cit and Gly on their surface. Subsequent biocompatibility tests confirm that MCF-Au-L NMs do not exert hemolytic activity (hemolysis < 5%). In addition, the CCK-8 viability assay tests indicate the higher sensitivity of cancerous cells (A549) to the photoactivity of MCF-Au compared to healthy Detroit 548 (D548) cell lines. We use advanced microscopy techniques, namely atomic force, fluorescence, and holotomography microscopies (AFM, FM, and HTM, respectively) to provide further insights into the nature of the observed photoactivity of MCF-Au-L NMs. In addition, in situ radiation, using a modified HTM microscope with an IR laser accessory, demonstrates the photoactivity of the MCF-Au NMs and their suitability for destroying cancerous cells through photodynamic therapy. The combined imaging capabilities demonstrate clear morphological changes, NMs internalization, and oxidative damage. Our results confirm that the fabricated multifunctional NMs exhibit high stability in aqueous solution, chemical solidity, superparamagnetic behavior, and effective IR responses, making them promising precursors for hybrid cancer therapy. Full article
(This article belongs to the Special Issue Toxicity of Nanoparticles: Second Edition)
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22 pages, 5623 KB  
Article
Lanthanides-Based Nanoparticles Conjugated with Rose Bengal for FRET-Mediated X-Ray-Induced PDT
by Batoul Dhaini, Joël Daouk, Hervé Schohn, Philippe Arnoux, Valérie Jouan-Hureaux, Albert Moussaron, Agnès Hagege, Mathilde Achard, Samir Acherar, Tayssir Hamieh and Céline Frochot
Pharmaceuticals 2025, 18(5), 672; https://doi.org/10.3390/ph18050672 - 1 May 2025
Cited by 1 | Viewed by 1619
Abstract
In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of [...] Read more.
In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of the poor penetration of visible light into tissues, which limits the efficacy of PDT in the treatment of deep-seated tumors. It is essential to optimize FRET efficiency by maximizing the overlap integral between donor emission and acceptor absorption and lengthening the duration of the donor emission. In this study, we optimized energy transfer between a scintillator (Sc) as a donor and a PS as an acceptor. Terbium (Tb) and Gadolinium (Gd) as Scs and Rose RB as a PS were chosen. The study of energy transfer between Tb, Gd and RB in solution and chelated on AGuIX NPs proved to be FRET-like. RB was conjugated directly onto AGuIX NPs (i.e., AGuIX Ln@RB), and the use of a spacer arm (i.e., AGuIX Ln@spacer arm-RB) increased FRET efficiency. Singlet oxygen production by these NPs was observed under UV–visible illumination and X-ray irradiation. The in vitro bioassay demonstrated 52% cell death of U-251MG derived from human malignant glioblastoma multiforme at a concentration of 1 μM RB after illumination and irradiation (2 Gy, 320 kV, 10 mA, 3 Gy/min at 47 cm). In addition, the RB-coupled NRP-1-targeting peptide (i.e., K(RB)DKPPR) was conjugated onto AGuIX NPs by a thiol-maleimide click chemistry reaction, and an affinity in the nM range was observed. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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14 pages, 3200 KB  
Article
Iodinated Copper–Cysteamine Nanoparticles as Radiosensitizers for Tumor Radiotherapy
by Miaomiao Zhang, Yu Yang, Ying Xu, Jie Wang and Shihong Li
Pharmaceutics 2025, 17(2), 149; https://doi.org/10.3390/pharmaceutics17020149 - 22 Jan 2025
Cited by 4 | Viewed by 2022
Abstract
Background/Objectives: Radiotherapy is a widely applied first-line clinical treatment modality of cancer. Copper–cysteamine (Cu-Cy) nanoparticles represent a new type of photosensitizer that demonstrates significant anti-tumor potential by X-ray-induced photodynamic therapy. Iodide is a high-Z element with superior X-ray absorption ability and has the [...] Read more.
Background/Objectives: Radiotherapy is a widely applied first-line clinical treatment modality of cancer. Copper–cysteamine (Cu-Cy) nanoparticles represent a new type of photosensitizer that demonstrates significant anti-tumor potential by X-ray-induced photodynamic therapy. Iodide is a high-Z element with superior X-ray absorption ability and has the β-decay radiotherapeutic nuclide, 131I, which emits Cherenkov light. In this study we aimed to investigate the X-ray-induced photodynamic therapy potential of iodinated Cu-Cy (Cu-Cy-I) nanoparticles and also explore the local treatment efficacy of 131I-labeled Cu-Cy-I ([131I]Cu-Cy-I) nanoparticles. Methods: The synthesis of [131I]Cu-Cy-I nanoparticles was performed with [131I]I anions. The in vitro radiobiological effects on tumor cells incubated with Cu-Cy-I nanoparticles by X-ray irradiation were investigated. The in vivo tumor growth-inhibitory effects of the combination of Cu-Cy-I nanoparticles with X-ray radiotherapy and [131I]Cu-Cy-I nanoparticles were evaluated with 4T1 tumor-xenografted mice. Results: The in vitro experiment results indicated that the X-ray irradiation with the presence of Cu-Cy-I nanoparticles produced a higher intracellular reactive oxygen species (ROS) level and more DNA damage of 4T1 cells and showed a stronger tumor cell killing ability compared to X-ray irradiation alone. The in vivo experimental results with 4T1 breast carcinoma-bearing mice showed that the combination of an intratumoral injection of Cu-Cy-I nanoparticles and X-ray radiotherapy enhanced the tumor growth-inhibitory effect and prolonged the mice’s lives. Conclusions: Cu-Cy-I nanoparticles have good potential as new radiosensitizers to enhance the efficacy of external X-ray radiotherapy. However, the efficacy of local treatment with [131I]Cu-Cy-I nanoparticles at a low 131I dose was not verified. The effective synthesis of smaller sizes of nanoparticles is necessary for further investigation of the radiotherapy potential of [131I]Cu-Cy-I nanoparticles. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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29 pages, 5745 KB  
Article
The Effect of a Photoactivated Ruthenium Nitrocomplex [RuCl(NO2)(dppb)(4,4-2 Mebipy)] on the Viability of Eukaryotic and Prokaryotic Cells, Including Bacterial Biofilms
by Alexandre L. Andrade, Aryane A. Pinheiro, Ellen A. Malveira, Isa M. F. Azevedo, Ana C. S. Gondim, Alzir A. Batista, João H. A. Neto, Eduardo E. Castellano, Alda K. M. Holanda, Mayron A. Vasconcelos and Edson H. Teixeira
Processes 2024, 12(12), 2841; https://doi.org/10.3390/pr12122841 - 11 Dec 2024
Cited by 1 | Viewed by 1280
Abstract
Antimicrobial resistance (AMR) is a critical global public health problem. Many bacterial pathogens use biofilm formation as their main pathogenicity mechanism, a practical tactic for surviving in natural settings and colonized host tissues. Research using ruthenium(II) complexes has demonstrated antibacterial action linked to [...] Read more.
Antimicrobial resistance (AMR) is a critical global public health problem. Many bacterial pathogens use biofilm formation as their main pathogenicity mechanism, a practical tactic for surviving in natural settings and colonized host tissues. Research using ruthenium(II) complexes has demonstrated antibacterial action linked to photodynamic therapy, an alternate method of microbial control. Thus, in this work, the photosensitive nitro complex [RuCl(NO2)(dppb)(4,4-Mebipy)] (I) was prepared and the X-ray structure was determined. Then, we investigated the antibacterial and antibiofilm activities, antibiotic-associated effects, and cytotoxicity. The results showed that complex I exhibited promising antimicrobial activity with MIC values ranging from 4 to 256 µg/mL and MBC from 4 to 32 µg/mL. The antimicrobial activity of this nitro complex was significantly enhanced with blue light irradiation, as confirmed by agarose gel electrophoresis of the pBR322 DNA, which must be related to the DNA cleavage promoted by the photorelease of NO. A synergistic effect against Staphylococcus aureus and Staphylococcus epidermidis strains was observed when combined with ampicillin, which exhibited FICI values from 0.186 to 0.311. Interestingly, complex I associated with tetracycline showed a synergistic effect only on Escherichia coli. Regarding biofilms, the irradiated complex I showed antibacterial activity against biofilm formation and mature biofilms. Furthermore, SEM and confocal analyses revealed changes in cell morphology and damage to the wall and plasma membrane. Complex I presented a percentage of hemolysis between 2 and 4%, and no cytotoxic effect was observed against murine dermal fibroblasts. In conclusion, the photoactivated ruthenium(II) complex showed antibacterial and antibiofilm activity against relevant bacteria. Full article
(This article belongs to the Special Issue Microbial Biofilms: Latest Advances and Prospects)
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18 pages, 3483 KB  
Article
Novel Flavin Mononucleotide-Functionalized Cerium Fluoride Nanoparticles for Selective Enhanced X-Ray-Induced Photodynamic Therapy
by Anastasia I. Kornienko, Maria A. Teplonogova, Marina P. Shevelyova, Matvei A. Popkov, Anton L. Popov, Vladimir E. Ivanov and Nelli R. Popova
J. Funct. Biomater. 2024, 15(12), 373; https://doi.org/10.3390/jfb15120373 - 10 Dec 2024
Cited by 4 | Viewed by 2038
Abstract
X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF3) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF3-FMN NPs has [...] Read more.
X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF3) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF3-FMN NPs has been developed, enabling the production of colloidal, spherical NPs with an approximate diameter of 100 nm, low polydispersity, and a high fluorescence quantum yield of 0.42. It has been demonstrated that CeF3-FMN NPs exhibit pH-dependent radiation-induced redox activity when exposed to X-rays. This activity results in the generation of reactive oxygen species, which is associated with the scintillation properties of cerium and the transfer of electrons to FMN. The synthesized NPs have been demonstrated to exhibit minimal cytotoxicity towards normal cells (NCTC L929 fibroblasts) but are more toxic to tumor cells (epidermoid carcinoma A431). Concurrently, the synthesized NPs (CeF3 and CeF3-FMN NPs) demonstrate a pronounced selective radiosensitizing effect on tumor cells at concentrations of 10−7 and 10−3 M, resulting in a significant reduction in their clonogenic activity, increasing radiosensitivity for cancer cells by 1.9 times following X-ray irradiation at a dose of 3 to 6 Gy. In the context of normal cells, these nanoparticles serve the function of antioxidants, maintaining a high level of clonogenic activity. Functional nanoscintillators on the basis of cerium fluoride can be used as part of the latest technologies for the treatment of tumors within the framework of X-PDT. Full article
(This article belongs to the Special Issue Advanced Photoresponsive Materials for Anticancer)
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16 pages, 4037 KB  
Article
Enhancing Effects of Olaparib by Alpha- and Beta-Emitting Radionuclides, X-Rays, and Ultraviolet A Light in Combination with Ortho-IodoHoechst in a Prostate Cancer Cell Model
by Andrea C. Luna Mass, Roswitha Runge, Kerstin Wetzig, Lisa Huebinger, Claudia Brogsitter and Joerg Kotzerke
Pharmaceuticals 2024, 17(11), 1450; https://doi.org/10.3390/ph17111450 - 30 Oct 2024
Cited by 2 | Viewed by 2337
Abstract
Background: New therapeutic strategies for metastatic castration-resistant prostate cancer (mCRPC) have been developed in the past to achieve the best response rates. Most recently, the use of combination therapies has been explored to optimize patient outcomes. Poly(ADP-ribose) polymerase inhibitors (PARPi) may help to [...] Read more.
Background: New therapeutic strategies for metastatic castration-resistant prostate cancer (mCRPC) have been developed in the past to achieve the best response rates. Most recently, the use of combination therapies has been explored to optimize patient outcomes. Poly(ADP-ribose) polymerase inhibitors (PARPi) may help to treat mCRPC more effectively. Objectives: This study aimed to determine whether the combination of a PARPi with different radiation qualities results in different levels of radiosensitization of PC-3 cells. Methods: The radiosensitizing potential of Olaparib in combination with 177Lu, 223Ra, X-rays and photodynamic therapy (PDT) using the UVA light-activated photosensitizer ortho-iodoHoechst33258 (oIH) was evaluated by determining the clonogenic survival, DNA damage and cell cycle analysis. Results: Here, we show that this combination strategy differentially sensitized PC-3 cells to different radiation qualities. The combination of 177Lu with Olaparib increased the numbers of persistent double-strand breaks (DSBs) by a factor of 3.3 and cell death in PC-3 cells. Overall, the β-emitter 177Lu indicated a higher radiosensitization efficacy compared to 223Ra, with X-rays corresponding to dose modification factors (DMF) of 1.77, 1.17 and 1.16 respectively. Even in the case of the α-emitter 223Ra, the effects were much less pronounced than for 177Lu. PARPi also showed a slight potentiation of the cytotoxic effects both in co-treatment with X-rays and with PDT. Conclusions: The results of our study indicate a potential role for Olaparib in further optimizing the PSMA radioligand therapy (PRLT) outcomes. However, further evaluation of the combination of PARPi with PRLT is needed to gain more insights into improving the benefit to patients suffering from mCRPC. Full article
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17 pages, 4400 KB  
Article
Preparation of Composite Hydrogels Based on Cysteine–Silver Sol and Methylene Blue as Promising Systems for Anticancer Photodynamic Therapy
by Dmitry V. Vishnevetskii, Fedor A. Metlin, Yana V. Andrianova, Elizaveta E. Polyakova, Alexandra I. Ivanova, Dmitry V. Averkin and Arif R. Mekhtiev
Gels 2024, 10(9), 577; https://doi.org/10.3390/gels10090577 - 5 Sep 2024
Cited by 2 | Viewed by 2298
Abstract
In this study, a novel supramolecular composite, “photogels”, was synthesized by mixing of cysteine–silver sol (CSS) and methylene blue (MB). A complex of modern physico-chemical methods of analysis such as viscosimetry, UV spectroscopy, dynamic and electrophoretic light scattering, scanning electron microscopy and energy-dispersive [...] Read more.
In this study, a novel supramolecular composite, “photogels”, was synthesized by mixing of cysteine–silver sol (CSS) and methylene blue (MB). A complex of modern physico-chemical methods of analysis such as viscosimetry, UV spectroscopy, dynamic and electrophoretic light scattering, scanning electron microscopy and energy-dispersive X-ray spectroscopy showed that MB molecules are uniformly localized mainly in the space between fibers of the gel-network formed by CSS particles. Molecules of the dye also bind with the surface of CSS particles by non-covalent interactions. This fact is reflected in the appearance of a synergistic anticancer effect of gels against human squamous cell carcinoma even in the absence of light irradiation. A mild toxic influence of hydrogels was observed in normal keratinocyte cells. Photodynamic exposure significantly increased gel activity, and there remained a synergistic effect. The study of free-radical oxidation in cells has shown that gels are not only capable of generating reactive oxygen species, but also have other targets of action. Flow cytometric analysis allowed us to find out that obtained hydrogels caused cell cycle arrest both without irradiation and with light exposure. The obtained gels are of considerable interest both from the point of view of academics and applied science, for example, in the photodynamic therapy of superficial neoplasms. Full article
(This article belongs to the Special Issue Synthesis and Applications of Hydrogels (2nd Edition))
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