Synthesis and physicochemical characterization of Lu and Sm sesquioxide nanoparticles by precipitation-calcination and pulsed laser ablation in liquids

Ancira-Cortez, Alejandra; Trujillo-Benítez, Diana; Jiménez-Mancilla, Nallely; Santos-Cuevas, Clara; Morales-Ávila, Enrique; Ferro-Flores, Guillermina

doi:10.1016/j.matchemphys.2021.125229

Cited by 8 publications

(11 citation statements)

References 41 publications

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“…TEM micrographs ( Figure 1 c) showed a spherical morphology with uniform and homogeneous distribution of the nanoparticles. The average diameter obtained from measurements of ~600 particles with the ImageJ program was 23.4 ± 7.9 nm with a monomodal and monodisperse distribution ( Figure 1 b); these results corroborated the formation and stability of the lutetium nanoparticles, in accordance with our previous reports [ 25 , 26 ]. With the average nanoparticle size value, and using the parameters reported for the crystalline cell of the nanomaterial (body-centered cubic space group la3, a ≈ 10.36 Å and a z = 16), the number of binding sites (Lu 3+ ) on the surface of the Lu 2 O 3 nanoparticles was calculated.…”

Section: Resultssupporting

confidence: 91%

“…Finally, the Lu-O stretching vibrational band, associated with the internal structure of the nanoparticles, was observed at 574 cm −1 . The Lu-O vibrational band also confirms that the formation of the final coordination complex was carried out by the chemical interaction between Lu 3+ and the electron pairs of the nitrogens (-NH) and oxygens (-OH) of DOTA [ 25 , 26 , 27 , 30 ].…”

Section: Resultsmentioning

confidence: 58%

“…Figure 1 shows the chemical characteristics of the formulated nanoparticles. Figure 1 a compares the IR spectrum of Lu−iFAP/iPSMA nanoparticles with regard to the employed raw materials: (1) infrared spectrum of lutetium oxide nanoparticles ( Figure 1 a1), where a narrow and intense band at 574 cm −1 of the Lu-O vibration was indicative of the nanometric size, the crystalline purity and the adequate crystallization of the nanomaterial [ 25 , 26 ]; and (2) infrared spectra of the targeting ligands iFAP ( Figure 1 a2) ( Figure A1 ) and iPSMA ( Figure 1 a3) ( Figure A2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, many research manuscripts have reported the synthesis of 177 Lu-labeled metallic and polymeric nanoparticles as radiotherapeutic systems [ 19 , 20 , 21 , 22 , 23 , 24 ]. However, our group reported the synthesis of [ 177 Lu]Lu 2 O 3 nanoparticles functionalized with peptides for the first time [ 25 , 26 ]. Previously, we found that [ 177 Lu]lutetium sesquioxide nanoparticles functionalized with FAP and PSMA inhibitor ligands (iFAP and iPSMA) ([ 177 Lu]Lu−iFAP/iPSMA) prevent HCT116 tumor progression in mice [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Toxicity Assessment of [177Lu]Lu−iFAP/iPSMA Nanoparticles Prepared under GMP-Compliant Radiopharmaceutical Processes

et al. 2022

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The fibroblast activation protein (FAP) is heavily expressed in fibroblasts associated with the tumor microenvironment, while the prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of malignant angiogenic processes. Previously, we reported that [177Lu]lutetium sesquioxide-iFAP/iPSMA nanoparticles ([177Lu]Lu−iFAP/iPSMA) inhibit HCT116 tumor progression in mice. Understanding the toxicity of [177Lu]Lu−iFAP/iPSMA in healthy tissues, as well as at the tissue and cellular level in pathological settings, is essential to demonstrate the nanosystem safety for treating patients. It is equally important to demonstrate that [177Lu]Lu−iFAP/iPSMA can be prepared under good manufacturing practices (GMP) with reproducible pharmaceutical-grade quality characteristics. This research aimed to prepare [177Lu]Lu−iFAP/iPSMA under GMP-compliant radiopharmaceutical processes and evaluate its toxicity in cell cultures and murine biological systems under pathological environments. [177Lu]Lu2O3 nanoparticles were formulated as radiocolloidal solutions with FAP and PSMA inhibitor ligands (iFAP and iPSMA), sodium citrate, and gelatin, followed by heating at 121 °C (103-kPa pressure) for 15 min. Three consecutive batches were manufactured. The final product was analyzed according to conventional pharmacopeial methods. The Lu content in the formulations was determined by X-ray fluorescence. [177Lu]Lu−iFAP/iPSMA performance in cancer cells was evaluated in vitro by immunofluorescence. Histopathological toxicity in healthy and tumor tissues was assessed in HCT116 tumor-bearing mice. Immunohistochemical assays were performed to corroborate FAP and PSMA tumor expression. Acute genotoxicity was evaluated using the micronuclei assay. The results showed that the batches manufactured under GMP conditions were reproducible. Radiocolloidal solutions were sterile and free of bacterial endotoxins, with radionuclidic and radiochemical purity greater than 99%. The lutetium content was 0.10 ± 0.02 mg/mL (0.9 GBq/mg). Significant inhibition of cell proliferation in vitro and in tumors was observed due to the accumulation of nanoparticles in the fibroblasts (FAP+) and neovasculature (PSMA+) of the tumor microenvironment. No histopathological damage was detected in healthy tissues. The data obtained in this research provide new evidence on the selective toxicity to malignant tumors and the absence of histological changes in healthy tissues after intravenous injection of [177Lu]Lu−iFAP/iPSMA in mammalian hosts. The easy preparation under GMP conditions and the toxicity features provide the added value needed for [177Lu]Lu−iFAP/iPSMA clinical translation.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxicity Assessment of [177Lu]Lu−iFAP/iPSMA Nanoparticles Prepared under GMP-Compliant Radiopharmaceutical Processes

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“…Nanoparticles intrinsically labeled using radionuclides such as 64 Cu, 72 As, 111 In, 153 Sm, 177 Lu and 198 Au, without employing chelators, have also been reported [ 34 , 35 , 36 , 37 ]. 198 Au emits a beta energy (0.96 MeV) ideal to penetrate within the tumor tissue up to 11 mm, providing cross-fire effects which can destroy the tumor cells [ 38 ].…”

Section: Radionuclides For Radiolabeling Various Nanoparticlesmentioning

confidence: 99%

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery

et al. 2022

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The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000′s, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ‘Nanosized delivery systems for radiopharmaceuticals’ involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications—all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor.

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Inorganic Radiolabeled Nanomaterials in Cancer Therapy: A Review

Lemaître

Burgoyne

Ooms

et al. 2022

ACS Appl. Nano Mater.

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Cancer, one of the leading causes of death worldwide, remains a challenge to treat. Over the last decades, targeted therapies have emerged as a way to selectively target and treat the affected cells, leaving the healthy ones intact. Nanomaterials, with their high surface area, ease of functionalization, and interesting physicochemical properties, are seen as promising carriers for therapeutic radionuclides. Their optical, electronic, and magnetic properties can be supplemented by the emitted ionizing radiation to form theranostic (therapeutic and diagnostic) or combined therapeutic agents. This review describes how different relevant therapeutic radionuclides can be incorporated into inorganic nanoconstructs to be delivered to the cancer cells and their impact on tumors. Different types of nanomaterials as well as multiple ways of incorporating radionuclides and their impact on the stability and both in vitro and in vivo performances are discussed.

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Synthesis and physicochemical characterization of Lu and Sm sesquioxide nanoparticles by precipitation-calcination and pulsed laser ablation in liquids

Cited by 8 publications

References 41 publications

Toxicity Assessment of [177Lu]Lu−iFAP/iPSMA Nanoparticles Prepared under GMP-Compliant Radiopharmaceutical Processes

Toxicity Assessment of [177Lu]Lu−iFAP/iPSMA Nanoparticles Prepared under GMP-Compliant Radiopharmaceutical Processes

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery

Inorganic Radiolabeled Nanomaterials in Cancer Therapy: A Review

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