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J. Nanotheranostics, Volume 4, Issue 2 (June 2023) – 3 articles

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30 pages, 6701 KiB  
Review
Self-Assembled Monolayers Derived from Positively Charged Adsorbates on Plasmonic Substrates for MicroRNA Delivery: A Review
by Johnson Hoang, Pooria Tajalli, Mina Omidiyan, Maria D. Marquez, Orawan Khantamat, Wirote Tuntiwechapikul, Chien-Hung Li, Arati Kohlhatkar, Hung-Vu Tran, Preethi H. Gunaratne and T. Randall Lee
J. Nanotheranostics 2023, 4(2), 171-200; https://doi.org/10.3390/jnt4020009 - 8 May 2023
Cited by 2 | Viewed by 3388
Abstract
MicroRNA (miRNA) has emerged as a promising alternative therapeutic treatment for cancer, but its delivery has been hindered by low cellular uptake and degradation during circulation. In this review, we discuss the various methods of delivering miRNA, including viral and non-viral delivery systems [...] Read more.
MicroRNA (miRNA) has emerged as a promising alternative therapeutic treatment for cancer, but its delivery has been hindered by low cellular uptake and degradation during circulation. In this review, we discuss the various methods of delivering miRNA, including viral and non-viral delivery systems such as liposomes and nanoparticles. We also examine the use of nanoparticles for miRNA-based diagnostics. We focus specifically on non-viral delivery systems utilizing coinage metals in the form of nanoparticles and the use of self-assembled monolayers (SAMs) as a method of surface modification. We review the use of SAMs for the conjugation and delivery of small noncoding ribonucleic acid (ncRNA), particularly SAMs derived from positively charged adsorbates to generate charged surfaces that can interact electrostatically with negatively charged miRNA. We also discuss the effects of the cellular uptake of gold and other plasmonic nanoparticles, as well as the challenges associated with the degradation of oligonucleotides. Our review highlights the potential of SAM-based systems as versatile and robust tools for delivering miRNA and other RNAs in vitro and in vivo and the need for further research to address the challenges associated with miRNA delivery and diagnostics. Full article
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<p>The canonical pathway of miRNA biogenesis. Most miRNA genes are transcribed by RNA polymerase II. The primary miRNAs (pri-miRNAs) are usually long, with a section of ~70 nt that forms a hairpin structure. The pri-miRNAs are cleaved into a miRNA precursor (pre-miRNA) in the nucleus by a microprocessor complex consisting of Drosha and DiGeorge Syndrome Critical Region 8 (DGCR8) protein. The pre-miRNA is then exported to the cytosol by the complex of Exportin-5 (XPO5) and Ran-GTP. In the cytoplasm, Ran-GTP is hydrolyzed to Ran-GDP, and the transport complex releases its pre-miRNA. The pre-miRNA is then cleaved by Dicer, in association with trans-activation response (TAR) RNA-binding protein (TRBP), to generate a mature miRNA duplex. The miRNA duplex-Dicer-TRBP complex then interacts with an Argonaute (AGO) protein to form the RISC-loading complex (RLC). AGO selects a guide strand, and the assembly of the RNA-induced silencing complex (RISC) proceeds. RISC recognizes the mRNA target through base-pairing with the miRNA, which then leads to mRNA degradation or translation inhibition.</p>
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<p>The base pairing of guide strand in RISC and its target mRNA. Schematic represents base pairing between a guide miRNA strand (purple) and a target mRNA (blue). The guide miRNA strand can be divided into four domains from 5′ to 3′. The seed region (g2–g8) is essential for target recognition. The central region (g9–g12) is important for mRNA and passenger strand cleavage. The 3′-supplementary region (g13–g17) stabilizes the complex with the mRNA target. The tail region (g18-3′ end) regulates the turnover of target cleavage and the fate of RISC. The 5′ end and 3′ end of the guide strand are anchored in the MID and PAZ domains of AGO2, respectively. Adapted with permission from reference [<a href="#B42-jnt-04-00009" class="html-bibr">42</a>]. Copyright 2022, Cell Press.</p>
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<p>Schematic illustrations depicting (<b>A</b>) normal growth, proliferation, differentiation, and cell death in normal tissue occurring through proper microRNA transcription; (<b>B</b>) defects at different stages of tumor suppressor miRNA biogenesis leading to the formation of oncoproteins; and (<b>C</b>) overexpression of oncogenic miRNA inhibiting expression of tumor suppressor protein and resulting in tumor formation. Reproduced with permission from reference [<a href="#B51-jnt-04-00009" class="html-bibr">51</a>]. Copyright 2006, Springer Nature.</p>
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<p>Depiction of the “proton sponge” mechanism after endocytosis of gold nanoparticles to escape the endosome. Reproduced with permission from reference [<a href="#B74-jnt-04-00009" class="html-bibr">74</a>]. Copyright 2009, Springer Nature.</p>
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<p>Schematic representation of the three essential parts of the adsorbate (terminal functional group, spacer, and headgroup on the substrate).</p>
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<p>(<b>A</b>) Illustration (Not to Scale) of the Preparation of miRNA−AuNP Conjugates for Delivering miRNAs to Cells. Reproduced with permission from reference [<a href="#B113-jnt-04-00009" class="html-bibr">113</a>]. Copyright 2012 American Chemical Society. (<b>B</b>) Gold-nanocage-based targeted nanocomplex formulation process and (<b>C</b>) NIR-laser-induced targeted gene-photothermal therapy using the nanocomplexes. Adapted with permission from reference [<a href="#B118-jnt-04-00009" class="html-bibr">118</a>]. Copyright 2016 Wiley.</p>
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<p>(<b>A</b>) Light-triggered release of miR-34a from nanoshells in TNBC cells. (<b>B</b>) Scheme depicting the process to coat NS with miRNA and Mpegsh. (<b>C</b>) Transmission electron micrograph of miR-co/NS. (<b>D</b>) Plasmon resonant extinction spectra comparing miRNA/NS conjugates to bare NS with peak extinction at 810 nm. (<b>E</b>) Hydrodynamic diameters (black outline) and zeta potential measurements (gray outline) of miRNA/NS conjugates and bare NS. (<b>F</b>) OliGreen analysis of miRNA loading on both miR34a/NS and miRco/NS. Reproduced with permission from reference [<a href="#B116-jnt-04-00009" class="html-bibr">116</a>]. Copyright 2021 American Chemical Society.</p>
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<p>(<b>A</b>) Schematic illustration of gold-nanoparticle-based NIR triggered sequential miR-21 inhibitor/Dox release with precise time interval for optimal combination therapy. (I–III) Formation of HGNP-based co-delivery system. D-P-HGNPs/21i entered cells through endocytosis (IV). Upon entering the tumor cells, miR-21i was released first (V), modulating the intrinsic state to a more chemosensitive state (VI). At the desired time, application of NIR laser triggered collapse of HGNPs and a burst release of doxorubicin (VII), activating two apoptosis signaling pathways, thereby inducing the synergistic apoptosis response (IX). (<b>B</b>) TEM images of HGNPs, D-P-HGNPs, D-P-HGNPs, and D-P-HGNPs-R. (<b>C</b>) Particle size measured by DLS. Adapted with permission from reference [<a href="#B115-jnt-04-00009" class="html-bibr">115</a>]. Copyright 2016 Elsevier.</p>
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<p>(<b>A</b>) Schematic illustration of synthesis of PolyGIONs and fluorescence images of Cy5-labeled miR-100 and antimiR-21-loaded CD-CS complexes. (<b>B</b>) Schematic representation of as-prepared polyGION structure and their various compositions. (<b>C</b>) TEM micrograph of GION. (<b>D</b>) GION coated with miR-100/antimiR-21 encapsulated CD-CS polymer layer, its EDS analysis, and corresponding images. (<b>E</b>) DLS measuring zeta potential and size of nanoparticles after each step of GION surface modification. (<b>F</b>) UV-vis spectra of as-prepared GION NS and its precursor nanoparticles. (<b>G</b>) Gel retardation assay for Cy5-miR-100/antimiR-21 encapsulation in CD-CS hybrid polymer and RNase protection assay for measuring the stability of encapsulated miRNAs in polyGION-CD-CS. Adapted with permission from reference [<a href="#B120-jnt-04-00009" class="html-bibr">120</a>]. Copyright 2019 Elsevier.</p>
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<p>Electrochemical biosensor constructed from DSN-assisted target recycling and TMSD-based catalytic hairpin assembly (CHA) where an amplified “b” and a weak “a” electrochemical signals are measured by differential pulse voltammetry (DPV) in the presence of miR-141 and in the absence of miR-141, repectively. Reprinted (adapted) with permission from [<a href="#B125-jnt-04-00009" class="html-bibr">125</a>]. Copyright 2018 American Chemical Society.</p>
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<p>(<b>A</b>) Purification of miRNA-107 by streptavidin-functionalized (blue part) magnetic beads (Dynabeads) followed by electrochemical measurements of the miRNA-deposited gold-loaded cubic nanoporous ferric oxide on the SPCE (light blue surface). Reprinted from [<a href="#B142-jnt-04-00009" class="html-bibr">142</a>], Copyright 2018, with permission from Elsevier. (<b>B</b>) Photonic resonator absorption microscopy (PRAM) utilizing magneto-plasmonic nanoparticles (MPNPs) on the photonic crystal (PC) surface constructed from (TiO<sub>2</sub>-SiO<sub>2</sub>). Reprinted (adapted) with permission from [<a href="#B141-jnt-04-00009" class="html-bibr">141</a>]. Copyright 2022 American Chemical Society.</p>
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<p>Assembly of AuNRs to create nanogap antennas.Reprinted with permission from Ref. [<a href="#B133-jnt-04-00009" class="html-bibr">133</a>]. Copyright 2020, Wiley-VCH GmbH.</p>
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<p>(<b>A</b>) Purification of target miRNA followed by hybridization to the Au film with immobilized DNA in an enzyme-free SPR biosensor. Reprinted from [<a href="#B123-jnt-04-00009" class="html-bibr">123</a>], Copyright 2017, with permission from Elsevier. (<b>B</b>) SPR biosensor constructed from AuNPs-MoS<sub>2</sub> nanocomposites to enhance SPR signal. Reprinted from [<a href="#B139-jnt-04-00009" class="html-bibr">139</a>], Copyright 2017, with permission from Elsevier.</p>
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<p>AgNPs in an enzyme-free SERS biosensor using mismatched CHA reactions. Reprinted from [<a href="#B87-jnt-04-00009" class="html-bibr">87</a>], Copyright 2019, with permission from Elsevier.</p>
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21 pages, 7123 KiB  
Review
Recent Advances in Noble Metal Nanoparticles for Cancer Nanotheranostics
by Dhiraj Kumar, Isha Mutreja and Ajeet Kaushik
J. Nanotheranostics 2023, 4(2), 150-170; https://doi.org/10.3390/jnt4020008 - 26 Apr 2023
Cited by 8 | Viewed by 3173
Abstract
The limitations of current treatment strategies for cancer management have prompted a significant shift in the research and development of new effective strategies exhibiting higher efficacy and acceptable side effects. In this direction, nanotheranostics has gained significant interest in recent years, combining the [...] Read more.
The limitations of current treatment strategies for cancer management have prompted a significant shift in the research and development of new effective strategies exhibiting higher efficacy and acceptable side effects. In this direction, nanotheranostics has gained significant interest in recent years, combining the diagnostic and therapeutic capabilities of nanostructures for efficient disease diagnosis, treatment, and management. Such nano-assisted platforms permit the site-specific release of bioactive cargo in a controlled fashion while permitting non-invasive real-time in situ monitoring. A plethora of materials has been developed as pharmacologically relevant nanoformulations for theranostic applications ranging from metallic to lipid and polymer-based composite systems, with each offering potential opportunities and its own limitations. To improve advancements with better clarity, the main focus of this review is to highlight the recent developments focusing on using different noble metal nanoparticles (noble MNPs) as cancer nanotheranostic agents, highlighting their properties, advantages, and potential modifications for their successful utilization in personalized medicine. The advantage of using noble metals (not all, but those with an atomic number ≥76) over metal NPs is their tendency to provide additional properties, such as X-ray attenuation and near-infrared activity. The combination of these properties translates to noble MNPs for therapeutic and diagnostic applications, independent of the need for additional active molecules. Through this review, we highlighted the potential application of all noble MNPs and the limited use of osmium, iridium, palladium, rhodium, and ruthenium metal NSs, even though they express similar physicochemical characteristics. The literature search was limited by PubMed, full-text availability, and studies including both in vitro and in vivo models. Full article
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Graphical abstract

Graphical abstract
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<p>(<bold>A</bold>) Represents the number of publications for each noble metal type during the respective year. (<bold>B</bold>) Schematic representation of engineered smart nanosystems and their scope in cancer targeting and diagnosis.</p>
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<p>(<bold>A</bold>,<bold>B</bold>) The TEM shape size and hydrodynamic diameter, along with surface charge on AuNPs, while the lysosome, Raman reporter, and combined confocal image of adenocarcinoma cells are shown in (<bold>C</bold>–<bold>E</bold>). The Raman spectra and peaks of the drug–Raman AuNPs in HT-adenocarcinoma cells with SERS peak at 508 cm<sup>–1</sup> shown in (<bold>F</bold>–<bold>H</bold>) represent the photon flux activity of luciferase in the tumor with NP-injected mice while (<bold>I</bold>) represents the activity in other organs. Images (<bold>J</bold>–<bold>L</bold>) show the hematoxylin and eosin (arrows represent tumor clones) (<bold>H</bold>,<bold>E</bold>) stain of sham-treated, AuNPs/Raman and drug–AuNPs/Raman-treated tumor; image reused with permission from reference [<xref ref-type="bibr" rid="B21-jnt-04-00008">21</xref>]. Copyright 2014, Elsevier. (<bold>M</bold>,<bold>N</bold>) The TEM shape and hydrodynamic diameter of surface-modified AuNPs, while (<bold>O</bold>) shows the ICP-MS analysis of AuNPs uptake by A431 cancer cells. (<bold>P</bold>,<bold>Q</bold>) The dual-energy CT image of a lung tumor after modified AuNP administration and CT quantification of Au in an in vivo tumor model, respectively; images reused with permission from reference [<xref ref-type="bibr" rid="B27-jnt-04-00008">27</xref>]. * <italic>p</italic> &lt; 0.05. Copyright 2018, Public Library of Science (PLOS).</p>
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<p>(<bold>A</bold>) The luminescence spectra of AgNPs-AuNCs, and (<bold>B</bold>,<bold>C</bold>) shows the TEM image of hybrid silver–gold nanoparticles and a high-resolution TEM image of the same, respectively. The microscopic fluorescence image of the control HeLa cells (<bold>D–F</bold>) show the bright field, fluorescent, and merged image, while (<bold>G</bold>–<bold>I</bold>) represent the same set of microscopic images post-NP treatment for 3 h. (<bold>J</bold>–<bold>L</bold>) The deconvolution fluorescence images (brightfield, fluorescent, and merged, respectively) of NP-treated HeLa cells after 3 h. (<bold>M</bold>,<bold>N</bold>) The NP internalization and high-magnification TEM images of HeLa cells with NPs. (<bold>O</bold>–<bold>Q</bold>) show the apoptosis percentage for control, AgNPs, and hybrid silver–gold NP-treated HeLa cells quantified by a Caspase 3 assay; the images are reused with permission from reference [<xref ref-type="bibr" rid="B52-jnt-04-00008">52</xref>]. Copyright 2016, Royal Society of Chemistry.</p>
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<p>TEM image for Pt nanoworms shown in (<bold>A</bold>,<bold>B</bold>) represents the cell viability of 4T1 cells in vitro with photothermal and radiation therapy. For the in vivo model, (<bold>C</bold>) shows the heating curve with/without nanoworms when exposed to a NIR source and (<bold>D</bold>) represents the IR thermal image of control and Pt nanoworm-administered mice. (<bold>E</bold>) The in vivo biodistribution of Pt nanoworms in 4T1 tumor-bearing mice and (<bold>F</bold>) demonstrates the change in tumor size for 4T1 tumor-bearing mice with combination therapy, while (<bold>G</bold>) shows a change in tumor volume within different groups. The images were reused with permission from reference [<xref ref-type="bibr" rid="B58-jnt-04-00008">58</xref>]. Copyright 2018, Royal Society of Chemistry. While in a hybrid Pt–Fe system for Dox delivery, (<bold>H</bold>,<bold>I</bold>) show the TEM image and high-resolution image of NPs. (<bold>J</bold>) Represents a change in GBM tumor size and (<bold>K</bold>) with actual GBM tumor photos for different groups. (<bold>L</bold>) Photos of GBM tumor size and (<bold>M</bold>) presents the MRI images with mouse brain in control, NPs, and drug-conjugated NPs (FePt-NB) groups. (<bold>N</bold>,<bold>O</bold>) demonstrates the change in tumor volume and the Kaplan– Meier survival curve. The images are reproduced with permission from reference [<xref ref-type="bibr" rid="B60-jnt-04-00008">60</xref>]. (* <italic>p</italic> &lt; 0.05, ** <italic>p</italic> &lt; 0.01, and *** <italic>p</italic> &lt; 0.001) Copyright 2021, American Chemical Society.</p>
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<p>Palladium nanoplates as a theranostic agent. The schematic representation of Pd@Au nanoplate synthesis and TEM images shown in (<bold>A</bold>,<bold>B</bold>) with solution color in (<bold>C</bold>,<bold>D</bold>) demonstrate the quantitative analysis for biodistribution of Pd@Au nanoplates in different organs at various time points, (<bold>d</bold>) represents HRTEM image of a Pd@Au nanoplate flat lying on the TEM. (<bold>E</bold>) The IR thermal imaging of control and tumor mice injected with nanoplates while (<bold>F</bold>) presents the photoacoustic imaging of the tumor site at different time points. (<bold>G</bold>–<bold>I</bold>) show the change in tumor volume, Kaplan–Meier survival curve, and photos of mice after photothermal treatment, respectively, administered with Pd nanoplates. Images are reused with permission from reference [<xref ref-type="bibr" rid="B73-jnt-04-00008">73</xref>]. Copyright 2014, Wiley.</p>
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<p>The TEM images and absorbance spectra for BSA-Ce6-modified hybrid iridium–manganese nanoparticles are shown in (<bold>A</bold>,<bold>B</bold>), respectively. (<bold>C</bold>) Represents the photothermal image of the Eppendorf with different concentrations of Ir: (<bold>D</bold>) is a schematic representation of oxygen generation with H<sub>2</sub>O<sub>2</sub> utilization, and (<bold>E</bold>) shows the quantitative data for O<sub>2</sub> generation using RDPP fluorescence quenching assay. (<bold>F</bold>–<bold>H</bold>) represent the CT image, MRI image, and PA image of the MDA-MB-231 tumor in a mouse model, respectively, injected with BSA-Ce6 conjugated IrO<sub>2</sub>/MnO<sub>2</sub> NPs. The fluorescence image of mice injected with free Ce6 and functionalized NPs shows the distribution (<bold>I</bold>) and the biodistribution of NPs in different organs in the mice model (<bold>J</bold>). The change in relative tumor volume is shown in (<bold>K</bold>), while (<bold>L</bold>) presents the photos of a tumor with the photothermal treatment. Images are reproduced with permission from reference [<xref ref-type="bibr" rid="B82-jnt-04-00008">82</xref>]. (** <italic>p</italic> &lt; 0.01, and *** <italic>p</italic> &lt; 0.001) Copyright 2020, Ivyspring International Publisher.</p>
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<p>(<bold>A</bold>) TEM image of PEGylated Rh NPs; (<bold>B</bold>,<bold>C</bold>) the absorbance spectra for NPs and O<sub>2</sub> generation by NPs in the presence of H<sub>2</sub>O<sub>2</sub>, respectively. (<bold>D</bold>) First image row shows the ROS staining of HUVECs cells with DCFH-DA, and second row, shows Calcein and PI staining showing dead and alive HUVECs cells with H<sub>2</sub>O<sub>2</sub> exposure and NPs treatment for cryoprotection and anti-inflammatory effect. (<bold>E</bold>) The hemolysis test at different NPs concentrations. (<bold>F</bold>) Photographs of colons extracted from various groups and histological images for H&amp;E, IL-4, TNF-a, and CD45 staining for the same groups show anti-inflammatory treatment of colitis with NPs treatment. (<bold>G</bold>) Photoacoustic image of the tumor (no NPs), tumor with NPs, and tumor with NPs + H<sub>2</sub>O<sub>2</sub>. (<bold>H</bold>) IR thermal image of CT-26 tumor with temperature gradient with NPs and laser exposure. (<bold>I</bold>,<bold>J</bold>) Photographs of CT-26 tumor with treatment and actual image of mice with tumor at day 16. Images reused with permission from reference [<xref ref-type="bibr" rid="B87-jnt-04-00008">87</xref>]. Copyright 2020, American Chemical Society.</p>
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<p>(<bold>A</bold>) Schematics showing the synthesis of OsTeNS by the solvothermal galvanic method, (<bold>B</bold>) the colloidal suspension color for TeNS and OsTeNS, and (<bold>C</bold>) the TEM image of OsTeNS. (<bold>D</bold>) A schematic representation of nanozymatic and photodynamic mechanism by Os-Te NS. (<bold>E</bold>,<bold>F</bold>) wavelength-dependent variability in temperature and heating/cooling cycle for OsTeNS when exposed to 808 nm laser, respectively. (<bold>G</bold>) Thermal imaging of RIL-175 tumor in mice injected with PBS and OsTeNS. (<bold>H</bold>,<bold>I</bold>) The change in relative tumor volume and Kaplan–Meier survival curve for tumor mice with NCTDI pentamodal therapy. Images reproduced with permission from reference [<xref ref-type="bibr" rid="B90-jnt-04-00008">90</xref>]. Copyright 2021, American Chemical Society.</p>
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<p>The synthesis schematics and TEM image of ultrasmall Ru nanodots are shown as (<bold>A</bold>,<bold>B</bold>), respectively. (<bold>C</bold>,<bold>D</bold>) The power and concentration-dependent increase in temperature in the presence of nanodots. (<bold>E</bold>) The nanodots were non-toxic to 4T1, CT26, and HUVECs cells up to 100 ug/mL (<bold>F</bold>) but caused cytotoxicity with nanodot-treated cells (4T1) were exposed with an 808 nm laser. (<bold>G</bold>) IR thermal imaging of the 4T1 tumor mice model with temperature gradient profile during the first 5 min and (<bold>H</bold>) the measured temperature for 4T1 tumor-bearing mice with PBS or Ru-Phen nanodots up to 5 h. The relative change in tumor volume has been represented in image (<bold>I</bold>) and the optical photographs of tumor-bearing mice undergoing PTT treatment (<bold>J</bold>). The biodistribution profile of Ru-Phen nanodots quantified using ICP-MS is shown in the image (<bold>K</bold>) at different time points. Image reused with permission from reference [<xref ref-type="bibr" rid="B109-jnt-04-00008">109</xref>]. Copyright 2019, Ivyspring International Publisher.</p>
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23 pages, 2896 KiB  
Review
Consolidation of Gold and Gadolinium Nanoparticles: An Extra Step towards Improving Cancer Imaging and Therapy
by Maria Anthi Kouri, Konstantina Polychronidou, Grigorios Loukas, Aikaterini Megapanou, Ioanna-Aglaia Vagena, Angelica M. Gerardos, Ellas Spyratou and Eftstathios P. Eftsathopoulos
J. Nanotheranostics 2023, 4(2), 127-149; https://doi.org/10.3390/jnt4020007 - 26 Apr 2023
Cited by 1 | Viewed by 2874
Abstract
The multifactorial nature of cancer still classifies the disease as one of the leading causes of death worldwide. Modern medical sciences are following an interdisciplinary approach that has been fueled by the nanoscale revolution of the past years. The exploitation of high-Z materials, [...] Read more.
The multifactorial nature of cancer still classifies the disease as one of the leading causes of death worldwide. Modern medical sciences are following an interdisciplinary approach that has been fueled by the nanoscale revolution of the past years. The exploitation of high-Z materials, in combination with ionizing or non-ionizing radiation, promises to overcome restrictions in medical imaging and to augment the efficacy of current therapeutic modalities. Gold nanoparticles (AuNPs) have proven their value among the scientific community in various therapeutic and diagnostic techniques. However, the high level of multiparametric demands of AuNP experiments in combination with their biocompatibility and cytotoxicity levels remain crucial issues. Gadolinium NPs (GdNPs), have presented high biocompatibility, low cytotoxicity, and excellent hemocompatibility, and have been utilized in MRI-guided radiotherapy, photodynamic and photothermal therapy, etc. Τhe utilization of gadolinium bound to AuNPs may be a promising alternative that would reduce phenomena, such as toxicity, aggregation, etc., and could create a multimodal in vivo contrast and therapeutic agent. This review highlights multi-functionalization strategies against cancer where gold and gadolinium NPs are implicated. Their experimental applications and limitations of the past 5 years will be analyzed in the hope of enlightening the benefits and drawbacks of their proper combination. Full article
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<p>Dark field microscopy depiction of (1) oral SCC head and neck cancer cells, (2) larynx SCC head and neck cancer cells after incubation with (<bold>a</bold>) non-matching antibody-coated gold nanorods and (<bold>b</bold>) matching UM-A9 antibody-coated gold nanorods at a scale bar of 10 μm. Reprinted with permission from reference [<xref ref-type="bibr" rid="B26-jnt-04-00007">26</xref>]. Copyright © 2008, ACS Publishing.</p>
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<p>Illustration of biodegradable gold nanoparticles where 5 nm AuNPs can be incorporated into a biodegradable polyphosphazene (PCPP) and, thus, lead into the creation of larger NPs with a potentially increased imaging contrast agent which can degrade in vivo and excrete the 5 nm AuNPs. Reprinted with permission from reference [<xref ref-type="bibr" rid="B18-jnt-04-00007">18</xref>]. Copyright © 2016, Elsevier.</p>
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<p>Possible applications of AuNPs in cancer therapy [<xref ref-type="bibr" rid="B43-jnt-04-00007">43</xref>].</p>
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<p>Depiction of targeted radiotherapy with the aid of PSMA-targeted AuNPs of different sizes for prostate cancer. Reprinted with permission from reference [<xref ref-type="bibr" rid="B44-jnt-04-00007">44</xref>]. Copyright 2019, The Royal Society of Chemistry.</p>
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<p>Schematic diagram of the application of Gd-HA NPs in the MRI detection of cartilage injuries [<xref ref-type="bibr" rid="B65-jnt-04-00007">65</xref>]. Licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.</p>
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<p>GdNP use in neutron capture reaction for therapeutic applications [<xref ref-type="bibr" rid="B85-jnt-04-00007">85</xref>]. Copyright 2016, Future Medicine Ltd.</p>
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