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Open AccessArticle

Radiofluorination of an Anionic, Azide-Functionalized Teroligomer by Copper-Catalyzed Azide-Alkyne Cycloaddition

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Michaela Schulz-Siegmund

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Peter Brust

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Michael C. Hacker

Nanomaterials 2023, 13(14), 2095; https://doi.org/10.3390/nano13142095 - 18 Jul 2023

Viewed by 527

Abstract

This study describes the synthesis, radiofluorination and purification of an anionic amphiphilic teroligomer developed as a stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NPs). As the stabilizing amphiphile accumulates on nanoparticle surfaces, the fluorine-18-labeled polymer should enable to track the distribution of the CaP-NPs [...] Read more.

This study describes the synthesis, radiofluorination and purification of an anionic amphiphilic teroligomer developed as a stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NPs). As the stabilizing amphiphile accumulates on nanoparticle surfaces, the fluorine-18-labeled polymer should enable to track the distribution of the CaP-NPs in brain tumors by positron emission tomography after application by convection-enhanced delivery. At first, an unmodified teroligomer was synthesized with a number average molecular weight of 4550 ± 20 Da by free radical polymerization of a defined composition of methoxy-PEG-monomethacrylate, tetradecyl acrylate and maleic anhydride. Subsequent derivatization of anhydrides with azido-TEG-amine provided an azido-functionalized polymer precursor (o14PEGMA-N₃) for radiofluorination. The ¹⁸F-labeling was accomplished through the copper-catalyzed cycloaddition of o14PEGMA-N₃ with diethylene glycol–alkyne-substituted heteroaromatic prosthetic group [¹⁸F]2, which was synthesized with a radiochemical yield (RCY) of about 38% within 60 min using a radiosynthesis module. The ¹⁸F-labeled polymer [¹⁸F]fluoro-o14PEGMA was obtained after a short reaction time of 2–3 min by using CuSO₄/sodium ascorbate at 90 °C. Purification was performed by solid-phase extraction on an anion-exchange cartridge followed by size-exclusion chromatography to obtain [¹⁸F]fluoro-o14PEGMA with a high radiochemical purity and an RCY of about 15%. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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Open AccessArticle

Total Bio-Based Material for Drug Delivery and Iron Chelation to Fight Cancer through Antimicrobial Activity

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Paolo Maria Riccobene

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Pio Maria Furneri

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Giuseppe Floresta

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Antonio Rescifina

Nanomaterials 2023, 13(14), 2036; https://doi.org/10.3390/nano13142036 - 10 Jul 2023

Viewed by 960

Abstract

Bacterial involvement in cancer’s development, along with their impact on therapeutic interventions, has been increasingly recognized. This has prompted the development of novel strategies to disrupt essential biological processes in microbial cells. Among these approaches, metal-chelating agents have gained attention for their ability [...] Read more.

Bacterial involvement in cancer’s development, along with their impact on therapeutic interventions, has been increasingly recognized. This has prompted the development of novel strategies to disrupt essential biological processes in microbial cells. Among these approaches, metal-chelating agents have gained attention for their ability to hinder microbial metal metabolism and impede critical reactions. Nanotechnology has also contributed to the antibacterial field by offering various nanomaterials, including antimicrobial nanoparticles with potential therapeutic and drug-delivery applications. Halloysite nanotubes (HNTs) are naturally occurring tubular clay nanomaterials composed of aluminosilicate kaolin sheets rolled multiple times. The aluminum and siloxane groups on the surface of HNTs enable hydrogen bonding with biomaterials, making them versatile in various domains, such as environmental sciences, wastewater treatment, nanoelectronics, catalytic studies, and cosmetics. This study aimed to create an antibacterial material by combining the unique properties of halloysite nanotubes with the iron-chelating capability of kojic acid. A nucleophilic substitution reaction involving the hydroxyl groups on the nanotubes’ surface was employed to functionalize the material using kojic acid. The resulting material was characterized using infrared spectroscopy (IR), thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM), and its iron-chelating ability was assessed. Furthermore, the potential for drug loading—specifically, with resveratrol and curcumin—was evaluated through ultraviolet (UV) analysis. The antibacterial assay was evaluated following CLSI guidelines. The results suggested that the HNTs–kojic acid formulation had great antibacterial activity against all tested pathogens. The outcome of this work yielded a novel bio-based material with dual functionality as a drug carrier and an antimicrobial agent. This innovative approach holds promise for addressing challenges related to bacterial infections, antibiotic resistance, and the development of advanced therapeutic interventions. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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Open AccessArticle

Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy

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Tainah Dorina Marforio

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Edoardo Jun Mattioli

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Francesco Zerbetto

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Matteo Calvaresi

Nanomaterials 2023, 13(11), 1770; https://doi.org/10.3390/nano13111770 - 31 May 2023

Viewed by 870

Abstract

Carboranes are promising agents for applications in boron neutron capture therapy (BNCT), but their hydrophobicity prevents their use in physiological environments. Here, by using reverse docking and molecular dynamics (MD) simulations, we identified blood transport proteins as candidate carriers of carboranes. Hemoglobin showed [...] Read more.

Carboranes are promising agents for applications in boron neutron capture therapy (BNCT), but their hydrophobicity prevents their use in physiological environments. Here, by using reverse docking and molecular dynamics (MD) simulations, we identified blood transport proteins as candidate carriers of carboranes. Hemoglobin showed a higher binding affinity for carboranes than transthyretin and human serum albumin (HSA), which are well-known carborane-binding proteins. Myoglobin, ceruloplasmin, sex hormone-binding protein, lactoferrin, plasma retinol-binding protein, thyroxine-binding globulin, corticosteroid-binding globulin and afamin have a binding affinity comparable to transthyretin/HSA. The carborane@protein complexes are stable in water and characterized by favorable binding energy. The driving force in the carborane binding is represented by the formation of hydrophobic interactions with aliphatic amino acids and BH-π and CH-π interactions with aromatic amino acids. Dihydrogen bonds, classical hydrogen bonds and surfactant-like interactions also assist the binding. These results (i) identify the plasma proteins responsible for binding carborane upon their intravenous administration, and (ii) suggest an innovative formulation for carboranes based on the formation of a carborane@protein complex prior to the administration. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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Open AccessArticle

Facile One-Pot Green Synthesis of Magneto-Luminescent Bimetallic Nanocomposites with Potential as Dual Imaging Agent

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Nanomaterials 2023, 13(6), 1027; https://doi.org/10.3390/nano13061027 - 13 Mar 2023

Viewed by 839

Abstract

Nanocomposites serving as dual (bimodal) probes have great potential in the field of bio-imaging. Here, we developed a simple one-pot synthesis for the reproducible generation of new luminescent and magnetically active bimetallic nanocomposites. The developed one-pot synthesis was performed in a sequential manner [...] Read more.

Nanocomposites serving as dual (bimodal) probes have great potential in the field of bio-imaging. Here, we developed a simple one-pot synthesis for the reproducible generation of new luminescent and magnetically active bimetallic nanocomposites. The developed one-pot synthesis was performed in a sequential manner and obeys the principles of green chemistry. Briefly, bovine serum albumin (BSA) was exploited to uptake Au (III) and Fe (II)/Fe (III) ions simultaneously. Then, Au (III) ions were transformed to luminescent Au nanoclusters embedded in BSA (AuNCs-BSA) and majority of Fe ions were bio-embedded into superparamagnetic iron oxide nanoparticles (SPIONs) by the alkalization of the reaction medium. The resulting nanocomposites, AuNCs-BSA-SPIONs, represent a bimodal nanoprobe. Scanning transmission electron microscopy (STEM) imaging visualized nanostructures with sizes in units of nanometres that were arranged into aggregates. Mössbauer spectroscopy gave direct evidence regarding SPION presence. The potential applicability of these bimodal nanoprobes was verified by the measurement of their luminescent features as well as magnetic resonance (MR) imaging and relaxometry. It appears that these magneto-luminescent nanocomposites were able to compete with commercial MRI contrast agents as MR displays the beneficial property of bright luminescence of around 656 nm (fluorescence quantum yield of 6.2 ± 0.2%). The biocompatibility of the AuNCs-BSA-SPIONs nanocomposite has been tested and its long-term stability validated. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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Open AccessArticle

Evaluation of Dosimetric Effect of Bone Scatter on Nanoparticle-Enhanced Orthovoltage Radiotherapy: A Monte Carlo Phantom Study

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Afia Sadiq

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James C. L. Chow

Nanomaterials 2022, 12(17), 2991; https://doi.org/10.3390/nano12172991 - 29 Aug 2022

Cited by 3 | Viewed by 953

Abstract

In nanoparticle (NP)-enhanced orthovoltage radiotherapy, bone scatter affected dose enhancement at the skin lesion in areas such as the forehead, chest wall, and knee. Since each of these treatment sites have a bone, such as the frontal bone, rib, or patella, underneath the [...] Read more.

In nanoparticle (NP)-enhanced orthovoltage radiotherapy, bone scatter affected dose enhancement at the skin lesion in areas such as the forehead, chest wall, and knee. Since each of these treatment sites have a bone, such as the frontal bone, rib, or patella, underneath the skin lesion and this bone is not considered in dose delivery calculations, uncertainty arises in the evaluation of dose enhancement with the addition of NPs in radiotherapy. To investigate the impact of neglecting the effect of bone scatter, Monte Carlo simulations based on heterogeneous phantoms were carried out to determine and compare the dose enhancement ratio (DER), when a bone was and was not present underneath the skin lesion. For skin lesions with added NPs, Monte Carlo simulations were used to calculate the DER values using different elemental NPs (gold, platinum, silver, iodine, as well as iron oxide), in varying NP concentrations (3–40 mg/mL), at two different photon beam energies (105 and 220 kVp). It was found that DER values at the skin lesion increased with the presence of bone when there was a higher atomic number of NPs, a higher NP concentration, and a lower photon beam energy. When comparing DER values with and without bone, using the same NP elements, NP concentration, and beam energy, differences were found in the range 0.04–3.55%, and a higher difference was found when the NP concentration increased. By considering the uncertainty in the DER calculation, the effect of bone scatter became significant to the dose enhancement (>2%) when the NP concentration was higher than 18 mg/mL. This resulted in an underestimation of dose enhancement at the skin lesion, when the bone underneath the tumour was neglected during orthovoltage radiotherapy. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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Review

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Open AccessEditor’s ChoiceReview

Metal-Polymer Nanoconjugates Application in Cancer Imaging and Therapy

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André Q. Figueiredo

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Carolina F. Rodrigues

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Nanomaterials 2022, 12(18), 3166; https://doi.org/10.3390/nano12183166 - 13 Sep 2022

Cited by 2 | Viewed by 1748

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Metallic-based nanoparticles present a unique set of physicochemical properties that support their application in different fields, such as electronics, medical diagnostics, and therapeutics. Particularly, in cancer therapy, the plasmonic resonance, magnetic behavior, X-ray attenuation, and radical oxygen species generation capacity displayed by metallic [...] Read more.

Metallic-based nanoparticles present a unique set of physicochemical properties that support their application in different fields, such as electronics, medical diagnostics, and therapeutics. Particularly, in cancer therapy, the plasmonic resonance, magnetic behavior, X-ray attenuation, and radical oxygen species generation capacity displayed by metallic nanoparticles make them highly promising theragnostic solutions. Nevertheless, metallic-based nanoparticles are often associated with some toxicological issues, lack of colloidal stability, and establishment of off-target interactions. Therefore, researchers have been exploiting the combination of metallic nanoparticles with other materials, inorganic (e.g., silica) and/or organic (e.g., polymers). In terms of biological performance, metal-polymer conjugation can be advantageous for improving biocompatibility, colloidal stability, and tumor specificity. In this review, the application of metallic-polymer nanoconjugates/nanohybrids as a multifunctional all-in-one solution for cancer therapy will be summarized, focusing on the physicochemical properties that make metallic nanomaterials capable of acting as imaging and/or therapeutic agents. Then, an overview of the main advantages of metal-polymer conjugation as well as the most common structural arrangements will be provided. Moreover, the application of metallic-polymer nanoconjugates/nanohybrids made of gold, iron, copper, and other metals in cancer therapy will be discussed, in addition to an outlook of the current solution in clinical trials. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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Open AccessReview

Nanoparticle-Based Therapeutics to Overcome Obstacles in the Tumor Microenvironment of Hepatocellular Carcinoma

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Nanomaterials 2022, 12(16), 2832; https://doi.org/10.3390/nano12162832 - 17 Aug 2022

Cited by 2 | Viewed by 1620

Abstract

Hepatocellular carcinoma (HCC) is still a main health concern around the world, with a rising incidence and high mortality rate. The tumor-promoting components of the tumor microenvironment (TME) play a vital role in the development and metastasis of HCC. TME-targeted therapies have recently [...] Read more.

Hepatocellular carcinoma (HCC) is still a main health concern around the world, with a rising incidence and high mortality rate. The tumor-promoting components of the tumor microenvironment (TME) play a vital role in the development and metastasis of HCC. TME-targeted therapies have recently drawn increasing interest in the treatment of HCC. However, the short medication retention time in TME limits the efficiency of TME modulating strategies. The nanoparticles can be elaborately designed as needed to specifically target the tumor-promoting components in TME. In this regard, the use of nanomedicine to modulate TME components by delivering drugs with protection and prolonged circulation time in a spatiotemporal manner has shown promising potential. In this review, we briefly introduce the obstacles of TME and highlight the updated information on nanoparticles that modulate these obstacles. Furthermore, the present challenges and future prospects of TME modulating nanomedicines will be briefly discussed. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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Open AccessReview

Recent Advances in Functionalized Nanoparticles in Cancer Theranostics

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Sarkar Siddique

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James C. L. Chow

Nanomaterials 2022, 12(16), 2826; https://doi.org/10.3390/nano12162826 - 17 Aug 2022

Cited by 25 | Viewed by 2421

Abstract

Cancer theranostics is the combination of diagnosis and therapeutic approaches for cancer, which is essential in personalized cancer treatment. The aims of the theranostics application of nanoparticles in cancer detection and therapy are to reduce delays in treatment and hence improve patient care. [...] Read more.

Cancer theranostics is the combination of diagnosis and therapeutic approaches for cancer, which is essential in personalized cancer treatment. The aims of the theranostics application of nanoparticles in cancer detection and therapy are to reduce delays in treatment and hence improve patient care. Recently, it has been found that the functionalization of nanoparticles can improve the efficiency, performance, specificity and sensitivity of the structure, and increase stability in the body and acidic environment. Moreover, functionalized nanoparticles have been found to possess a remarkable theranostic ability and have revolutionized cancer treatment. Each cancer treatment modality, such as MRI-guided gene therapy, MRI-guided thermal therapy, magnetic hyperthermia treatment, MRI-guided chemotherapy, immunotherapy, photothermal and photodynamic therapy, has its strengths and weaknesses, and combining modalities allows for a better platform for improved cancer control. This is why cancer theranostics have been investigated thoroughly in recent years and enabled by functionalized nanoparticles. In this topical review, we look at the recent advances in cancer theranostics using functionalized nanoparticles. Through understanding and updating the development of nanoparticle-based cancer theranostics, we find out the future challenges and perspectives in this novel type of cancer treatment. Full article

(This article belongs to the Special Issue Applications of Nanomaterials in Biomedical Imaging and Cancer Therapy II)

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