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Keywords = lutetium oxide nanoparticles

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35 pages, 1042 KiB  
Review
Potential Applications of Rare Earth Metal Nanoparticles in Biomedicine
by Svetlana A. Titova, Maria P. Kruglova, Victor A. Stupin, Natalia E. Manturova and Ekaterina V. Silina
Pharmaceuticals 2025, 18(2), 154; https://doi.org/10.3390/ph18020154 - 24 Jan 2025
Cited by 6 | Viewed by 2651
Abstract
In recent years, the world scientific community has shown increasing interest in rare earth metals in general and their nanoparticles in particular. Medicine and pharmaceuticals are no exception in this matter. In this review, we have considered the main opportunities and potential applications [...] Read more.
In recent years, the world scientific community has shown increasing interest in rare earth metals in general and their nanoparticles in particular. Medicine and pharmaceuticals are no exception in this matter. In this review, we have considered the main opportunities and potential applications of rare earth metal (gadolinium, europium, ytterbium, holmium, lutetium, dysprosium, erbium, terbium, thulium, scandium, yttrium, lanthanum, europium, neodymium, promethium, samarium, praseodymium, cerium) nanoparticles in biomedicine, with data ranging from single reports of effects found in vitro to numerous independent in vivo studies, as well as a number of challenges to their potential for wider application. The main areas of application of rare earth metals, including in the future, are diagnosis and treatment of malignant neoplasms, therapy of infections, as well as the use of antioxidant and regenerative properties of a number of nanoparticles. These applications are determined both by the properties of rare earth metal nanoparticles themselves and the need to search for new approaches to solve a number of urgent biomedical and public health problems. Oxide forms of lanthanides are most often used in biomedicine due to their greatest biocompatibility and nanoscale size, providing penetration through biological membranes. However, the existing contradictory or insufficient data on acute and chronic toxicity of lanthanides still make their widespread use difficult. There are various modification methods (addition of excipients, creation of nanocomposites, and changing the morphology of particles) that can reduce these effects. At the same time, despite the use of some representatives of lanthanides in clinical practice, further studies to establish the full range of pharmacological and toxic effects, as well as the search for approaches to modify nanoparticles remain relevant. Full article
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37 pages, 9132 KiB  
Article
177Lu-Labeled Iron Oxide Nanoparticles Functionalized with Doxorubicin and Bevacizumab as Nanobrachytherapy Agents against Breast Cancer
by Evangelia-Alexandra Salvanou, Argiris Kolokithas-Ntoukas, Danai Prokopiou, Maria Theodosiou, Eleni Efthimiadou, Przemysław Koźmiński, Stavros Xanthopoulos, Konstantinos Avgoustakis and Penelope Bouziotis
Molecules 2024, 29(5), 1030; https://doi.org/10.3390/molecules29051030 - 27 Feb 2024
Cited by 8 | Viewed by 2406
Abstract
The use of conventional methods for the treatment of cancer, such as chemotherapy or radiotherapy, and approaches such as brachytherapy in conjunction with the unique properties of nanoparticles could enable the development of novel theranostic agents. The aim of our current study was [...] Read more.
The use of conventional methods for the treatment of cancer, such as chemotherapy or radiotherapy, and approaches such as brachytherapy in conjunction with the unique properties of nanoparticles could enable the development of novel theranostic agents. The aim of our current study was to evaluate the potential of iron oxide nanoparticles, coated with alginic acid and polyethylene glycol, functionalized with the chemotherapeutic agent doxorubicin and the monoclonal antibody bevacizumab, to serve as a nanoradiopharmaceutical agent against breast cancer. Direct radiolabeling with the therapeutic isotope Lutetium-177 (177Lu) resulted in an additional therapeutic effect. Functionalization was accomplished at high percentages and radiolabeling was robust. The high cytotoxic effect of our radiolabeled and non-radiolabeled nanostructures was proven in vitro against five different breast cancer cell lines. The ex vivo biodistribution in tumor-bearing mice was investigated with three different ways of administration. The intratumoral administration of our functionalized radionanoconjugates showed high tumor accumulation and retention at the tumor site. Finally, our therapeutic efficacy study performed over a 50-day period against an aggressive triple-negative breast cancer cell line (4T1) demonstrated enhanced tumor growth retention, thus identifying the developed nanoparticles as a promising nanobrachytherapy agent against breast cancer. Full article
(This article belongs to the Special Issue Novel Targeted Radiopharmaceuticals for Diagnosis and Therapy)
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25 pages, 2374 KiB  
Review
Molecularly Targeted Lanthanide Nanoparticles for Cancer Theranostic Applications
by Guillermina Ferro-Flores, Alejandra Ancira-Cortez, Blanca Ocampo-García and Laura Meléndez-Alafort
Nanomaterials 2024, 14(3), 296; https://doi.org/10.3390/nano14030296 - 31 Jan 2024
Cited by 12 | Viewed by 3882
Abstract
Injectable colloidal solutions of lanthanide oxides (nanoparticles between 10 and 100 nm in size) have demonstrated high biocompatibility and no toxicity when the nanoparticulate units are functionalized with specific biomolecules that molecularly target various proteins in the tumor microenvironment. Among the proteins successfully [...] Read more.
Injectable colloidal solutions of lanthanide oxides (nanoparticles between 10 and 100 nm in size) have demonstrated high biocompatibility and no toxicity when the nanoparticulate units are functionalized with specific biomolecules that molecularly target various proteins in the tumor microenvironment. Among the proteins successfully targeted by functionalized lanthanide nanoparticles are folic receptors, fibroblast activation protein (FAP), gastrin-releasing peptide receptor (GRP-R), prostate-specific membrane antigen (PSMA), and integrins associated with tumor neovasculature. Lutetium, samarium, europium, holmium, and terbium, either as lanthanide oxide nanoparticles or as nanoparticles doped with lanthanide ions, have demonstrated their theranostic potential through their ability to generate molecular images by magnetic resonance, nuclear, optical, or computed tomography imaging. Likewise, photodynamic therapy, targeted radiotherapy (neutron-activated nanoparticles), drug delivery guidance, and image-guided tumor therapy are some examples of their potential therapeutic applications. This review provides an overview of cancer theranostics based on lanthanide nanoparticles coated with specific peptides, ligands, and proteins targeting the tumor microenvironment. Full article
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17 pages, 10055 KiB  
Article
Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors
by Dragana Stanković, Magdalena Radović, Aljoša Stanković, Marija Mirković, Aleksandar Vukadinović, Milica Mijović, Zorana Milanović, Miloš Ognjanović, Drina Janković, Bratislav Antić, Sanja Vranješ-Đurić, Miroslav Savić and Željko Prijović
Pharmaceutics 2023, 15(7), 1943; https://doi.org/10.3390/pharmaceutics15071943 - 13 Jul 2023
Cited by 6 | Viewed by 2367
Abstract
As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) [...] Read more.
As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (177Lu), generating 177Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by 177Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 µg/50 µL of 177Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 µg/50 µL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 µg/50 µL did not significantly benefit the therapy. Histopathology analysis revealed that the 177Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, 177Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy. Full article
(This article belongs to the Topic Innovative Radiation Therapies)
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21 pages, 3573 KiB  
Article
Preliminary Evaluation of Iron Oxide Nanoparticles Radiolabeled with 68Ga and 177Lu as Potential Theranostic Agents
by Evangelia-Alexandra Salvanou, Argiris Kolokithas-Ntoukas, Christos Liolios, Stavros Xanthopoulos, Maria Paravatou-Petsotas, Charalampos Tsoukalas, Konstantinos Avgoustakis and Penelope Bouziotis
Nanomaterials 2022, 12(14), 2490; https://doi.org/10.3390/nano12142490 - 20 Jul 2022
Cited by 17 | Viewed by 3077
Abstract
Theranostic radioisotope pairs such as Gallium-68 (68Ga) for Positron Emission Tomography (PET) and Lutetium-177 (177Lu) for radioisotopic therapy, in conjunction with nanoparticles (NPs), are an emerging field in the treatment of cancer. The present work aims to demonstrate the [...] Read more.
Theranostic radioisotope pairs such as Gallium-68 (68Ga) for Positron Emission Tomography (PET) and Lutetium-177 (177Lu) for radioisotopic therapy, in conjunction with nanoparticles (NPs), are an emerging field in the treatment of cancer. The present work aims to demonstrate the ability of condensed colloidal nanocrystal clusters (co-CNCs) comprised of iron oxide nanoparticles, coated with alginic acid (MA) and stabilized by a layer of polyethylene glycol (MAPEG) to be directly radiolabeled with 68Ga and its therapeutic analog 177Lu. 68Ga/177Lu- MA and MAPEG were investigated for their in vitro stability. The biocompatibility of the non-radiolabeled nanoparticles, as well as the cytotoxicity of MA, MAPEG, and [177Lu]Lu-MAPEG were assessed on 4T1 cells. Finally, the ex vivo biodistribution of the 68Ga-labeled NPs as well as [177Lu]Lu-MAPEG was investigated in normal mice. Radiolabeling with both radioisotopes took place via a simple and direct labelling method without further purification. Hemocompatibility was verified for both NPs, while MTT studies demonstrated the non-cytotoxic profile of the nanocarriers and the dose-dependent toxicity for [177Lu]Lu-MAPEG. The radiolabeled nanoparticles mainly accumulated in RES organs. Based on our preliminary results, we conclude that MAPEG could be further investigated as a theranostic agent for PET diagnosis and therapy of cancer. Full article
(This article belongs to the Special Issue Nanoparticles in Diagnostic and Therapeutic Applications)
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17 pages, 3529 KiB  
Article
Targeted Endoradiotherapy with Lu2O3-iPSMA/-iFAP Nanoparticles Activated by Neutron Irradiation: Preclinical Evaluation and First Patient Image
by Myrna Luna-Gutiérrez, Blanca Ocampo-García, Nallely Jiménez-Mancilla, Alejandra Ancira-Cortez, Diana Trujillo-Benítez, Tania Hernández-Jiménez, Gerardo Ramírez-Nava, Rodrigo Hernández-Ramírez, Clara Santos-Cuevas and Guillermina Ferro-Flores
Pharmaceutics 2022, 14(4), 720; https://doi.org/10.3390/pharmaceutics14040720 - 27 Mar 2022
Cited by 14 | Viewed by 3003
Abstract
Prostate-specific membrane antigen (PSMA) is expressed in a variety of cancer cells, while the fibroblast activation protein (FAP) is expressed in the microenvironment of tumors. Previously, we reported the ability of iPSMA and iFAP ligands to specifically target PSMA and FAP proteins, as [...] Read more.
Prostate-specific membrane antigen (PSMA) is expressed in a variety of cancer cells, while the fibroblast activation protein (FAP) is expressed in the microenvironment of tumors. Previously, we reported the ability of iPSMA and iFAP ligands to specifically target PSMA and FAP proteins, as well as the preparation of stable 177Lu2O3 nanoparticles (<100 nm) functionalized with target-specific peptides. This research aimed to evaluate the dosimetry and therapeutic response of Lu2O3-iPSMA and Lu2O3-iFAP nanoparticles activated by neutron irradiation to demonstrate their potential for theranostic applications in nuclear medicine. The biokinetic behavior, radiation absorbed dose, and metabolic activity ([18F]FDG/micro-PET, SUV) in preclinical tumor tissues (athymic mice), following treatment with 177Lu2O3-iPSMA, 177Lu2O3-iFAP or 177Lu2O3 nanoparticles, were assessed. One patient with multiple colorectal liver metastases (PSMA-positive) received 177Lu2O3-iPSMA under a “compassionate use” protocol. Results indicated no significant difference (p < 0.05) between 177Lu2O3-iPSMA and 177Lu2O3-iFAP, regarding tumor radiation absorbed doses (105 ± 14 Gy, 99 ± 12 Gy and 58 ± 7 Gy for 177Lu2O3-iPSMA, 177Lu2O3-iFAP, and 177Lu2O3, respectively) and tumor metabolic activity (SUV of 0.421 ± 0.092, 0.375 ± 0.104 and 1.821 ± 0.891 for 177Lu2O3-iPSMA, 177Lu2O3-iFAP, and 177Lu2O3, respectively) in mice after treatment, which correlated with the observed therapeutic response. 177Lu2O3-iPSMA and 177Lu2O3-iFAP significantly inhibited tumor progression, due to the prolonged tumor retention and a combination of 177Lu radiotherapy and iPSMA or iFAP molecular recognition. There were negligible uptake values in non-target tissues and no evidence of liver and renal toxicity. The doses received by the patient’s liver metastases (42–210 Gy) demonstrated the potential of 177Lu2O3-iPSMA for treating colorectal liver metastases. Full article
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