Research

Jump to: Review

17 pages, 2389 KiB

Open AccessArticle

A New Generation of Ultrasmall Nanoparticles Inducing Sensitization to Irradiation and Copper Depletion to Overcome Radioresistant and Invasive Cancers

by Paul Rocchi, Delphine Brichart-Vernos, François Lux, Isabelle Morfin, Laurent David, Claire Rodriguez-Lafrasse and Olivier Tillement

Pharmaceutics 2022, 14(4), 814; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040814 - 07 Apr 2022

Cited by 7 | Viewed by 2075

Abstract

An emerging target to overcome cancer resistance to treatments is copper, which is upregulated in a wide variety of tumors and may be associated with cancer progression and metastases. The aim of this study was to develop a multimodal ultrasmall nanoparticle, CuPRiX, based [...] Read more.

An emerging target to overcome cancer resistance to treatments is copper, which is upregulated in a wide variety of tumors and may be associated with cancer progression and metastases. The aim of this study was to develop a multimodal ultrasmall nanoparticle, CuPRiX, based on the clinical AGuIX nanoparticle made of the polysiloxane matrix on which gadolinium chelates are grafted. Such hybrid nanoparticles allow: (i) a localized depletion of copper in tumors to prevent tumor cell dissemination and metastasis formation and (ii) an increased sensitivity of the tumor to radiotherapy (RT) due to the presence of high Z gadolinium (Gd) atoms. CuPRiX nanoparticles are obtained by controlled acidification of AGuIX nanoparticles. They were evaluated in vitro on two cancer cell lines (lung and head and neck) using the scratch-wound assay and clonogenic cell survival assay. They were able to reduce cell migration and invasion and displayed radiosensitizing properties. Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures

Figure 1

18 pages, 3349 KiB

Open AccessArticle

Mass Cytometry Exploration of Immunomodulatory Responses of Human Immune Cells Exposed to Silver Nanoparticles

by Jiwon Bae, My Ha, Haribalan Perumalsamy, Yangsoon Lee, Jaewoo Song and Tae-Hyun Yoon

Pharmaceutics 2022, 14(3), 630; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14030630 - 12 Mar 2022

Cited by 3 | Viewed by 2746

Abstract

Increasing production and application of silver nanoparticles (Ag NPs) have raised concerns on their possible adverse effects on human health. However, a comprehensive understanding of their effects on biological systems, especially immunomodulatory responses involving various immune cell types and biomolecules (e.g., cytokines and [...] Read more.

Increasing production and application of silver nanoparticles (Ag NPs) have raised concerns on their possible adverse effects on human health. However, a comprehensive understanding of their effects on biological systems, especially immunomodulatory responses involving various immune cell types and biomolecules (e.g., cytokines and chemokines), is still incomplete. In this study, a single-cell-based, high-dimensional mass cytometry approach is used to investigate the immunomodulatory responses of Ag NPs using human peripheral blood mononuclear cells (hPBMCs) exposed to poly-vinyl-pyrrolidone (PVP)-coated Ag NPs of different core sizes (i.e., 10-, 20-, and 40-nm). Although there were no severe cytotoxic effects observed, ^PVPAg¹⁰ and ^PVPAg²⁰ were excessively found in monocytes and dendritic cells, while ^PVPAg⁴⁰ displayed more affinity with B cells and natural killer cells, thereby triggering the release of proinflammatory cytokines such as IL-2, IL-17A, IL-17F, MIP1β, TNFα, and IFNγ. Our findings indicate that under the exposure conditions tested in this study, Ag NPs only triggered the inflammatory responses in a size-dependent manner rather than induce cytotoxicity in hPBMCs. Our study provides an appropriate ex vivo model to better understand the human immune responses against Ag NP at a single-cell level, which can contribute to the development of targeted drug delivery, vaccine developments, and cancer radiotherapy treatments. Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures

Graphical abstract

16 pages, 3690 KiB

Open AccessArticle

NVCL-Based Galacto-Functionalized and Thermosensitive Nanogels with GNRDs for Chemo/Photothermal-Therapy

by Mirian A. González-Ayón, Jacob Licea-Rodriguez, Eugenio R. Méndez and Angel Licea-Claverie

Pharmaceutics 2022, 14(3), 560; https://doi.org/10.3390/pharmaceutics14030560 - 03 Mar 2022

Cited by 6 | Viewed by 1865

Abstract

Dual-function nanogels (particle size from 98 to 224 nm) synthesized via surfactant-free emulsion polymerization (SFEP) were tested as smart carriers toward synergistic chemo- and photothermal therapy. Cisplatin (CDDP) or doxorubicin (DOX) and gold nanorods (GNRDs) were loaded into galacto-functionalized PNVCL-based nanogels, where the [...] Read more.

Dual-function nanogels (particle size from 98 to 224 nm) synthesized via surfactant-free emulsion polymerization (SFEP) were tested as smart carriers toward synergistic chemo- and photothermal therapy. Cisplatin (CDDP) or doxorubicin (DOX) and gold nanorods (GNRDs) were loaded into galacto-functionalized PNVCL-based nanogels, where the encapsulation efficiency for CDDP and DOX was around 64 and 52%, respectively. PNVCL-based nanogels were proven to be an efficient delivery vehicle under conditions that mimic the tumor site in vitro. The release of CDDP or DOX was slower at pH 7.4 and 37 °C than at tumor conditions of pH 6 and 40 °C. On the other hand, in the systems with GNRDs at pH 7.4 and 37 °C, the sample was irradiated with a 785 nm laser for 10 min every hour, obtaining that the release profiles were even higher than in the conditions that simulated a cancer tissue (without irradiation). Thus, the present study demonstrates the synergistic effect of chemo- and photothermal therapy as a promising dual function in the potential future use of PNVCL nanogels loaded with GNRDs and CDDP/DOX to achieve an enhanced chemo/phototherapy in vivo. Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures

Figure 1

18 pages, 2929 KiB

Open AccessArticle

Nanotechnology Driven Cancer Chemoradiation: Exploiting the Full Potential of Radiotherapy with a Unique Combination of Gold Nanoparticles and Bleomycin

by Ocean Han, Kyle Bromma, Nicholas Palmerley, Ariadne T. Bido, Mesa Monica, Abdulaziz Alhussan, Perry L. Howard, Alexandre G. Brolo, Wayne Beckham, Abraham S. Alexander and Devika B. Chithrani

Pharmaceutics 2022, 14(2), 233; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020233 - 20 Jan 2022

Cited by 5 | Viewed by 2452

Abstract

One of the major issues in current radiotherapy (RT) is the associated normal tissue toxicity. Enhancement of the RT effect with novel radiosensitizers can address this need. In this study, gold nanoparticles (GNPs) and bleomycin (BLM) were used as a unique combination of [...] Read more.

One of the major issues in current radiotherapy (RT) is the associated normal tissue toxicity. Enhancement of the RT effect with novel radiosensitizers can address this need. In this study, gold nanoparticles (GNPs) and bleomycin (BLM) were used as a unique combination of radiosensitizers. GNPs offer a two-fold promise as a delivery vehicle for BLM and as a radiosensitizing agent. In this study, GNPs were functionalized and complexed with BLM using a gold-thiol bond (denoted GNP-BLM). Our results show that there was a 40% and 10% decrease in cell growth with GNP-BLM vs. free BLM for the MIA PaCa-2 and PC-3 cell lines, respectively. Testing the GNP-BLM platform with RT showed an 84% and 13% reduction in cell growth in MIA PaCa-2 cells treated with GNP-BLM and GNPs, respectively. Similar results were seen with PC-3 cells. The efficacy of this approach was verified by mapping DNA double-strand breaks (DSBs) as well. Therefore, this proposed incorporation of nanomedicine with RT is promising in achieving a significantly higher therapeutic ratio which is necessary to make a paradigm change to the current clinical approach. Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures

Graphical abstract

42 pages, 14062 KiB

Open AccessArticle

Incorporation of Low Concentrations of Gold Nanoparticles: Complex Effects on Radiation Response and Fate of Cancer Cells

by Lucie Dobešová, Theresa Gier, Olga Kopečná, Eva Pagáčová, Tomáš Vičar, Felix Bestvater, Jiří Toufar, Alena Bačíková, Pavel Kopel, Radek Fedr, Georg Hildenbrand, Iva Falková, Martin Falk and Michael Hausmann

Pharmaceutics 2022, 14(1), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010166 - 11 Jan 2022

Cited by 7 | Viewed by 3007

Abstract

(1) Background: In oncology research, a long-standing discussion exists about pros and cons of metal nanoparticle-enhanced radiotherapy and real mechanisms behind the tumor cell response to irradiation (IR) in presence of gold nanoparticles (GNPs). A better understanding of this response is, however, [...] Read more.

(1) Background: In oncology research, a long-standing discussion exists about pros and cons of metal nanoparticle-enhanced radiotherapy and real mechanisms behind the tumor cell response to irradiation (IR) in presence of gold nanoparticles (GNPs). A better understanding of this response is, however, necessary to develop more efficient and safety nanoparticle (NP) types designed to disturb specific processes in tumor cells. (2) Aims and Methods: We combined 3D confocal microscopy and super-resolution single molecule localization microscopy (SMLM) to analyze, at the multiscale, the early and late effects of 10 nm-GNPs on DNA double strand break (DSB) induction and repair in tumor cells exposed to different doses of photonic low-LET (linear energy transfer) radiation. The results were correlated to different aspects of short and long-term cell viability. SkBr3 breast cancer cells (selected for the highest incidence of this cancer type among all cancers in women, and because most breast tumors are treated with IR) were incubated with low concentrations of GNPs and irradiated with ⁶⁰Co γ-rays or 6 MV X-rays. In numerous post-irradiation (PI) times, ranging from 0.5 to 24 h PI, the cells were spatially (3D) fixed and labeled with specific antibodies against γH2AX, 53BP1 and H3K9me3. The extent of DSB induction, multi-parametric micro- and nano-morphology of γH2AX and 53BP1 repair foci, DSB repair kinetics, persistence of unrepaired DSBs, nanoscale clustering of γH2AX and nanoscale (hetero)chromatin re-organization were measured by means of the mentioned microscopy techniques in dependence of radiation dose and GNP concentration. (3) Results: The number of γH2AX/53BP1 signals increased after IR and an additional increase was observed in GNP-treated (GNP(+)) cells compared to untreated controls. However, this phenomenon reflected slight expansion of the G2-phase cell subpopulation in irradiated GNP(+) specimens instead of enhanced DNA damage induction by GNPs. This statement is further supported by some micro- and nano-morphological parameters of γH2AX/53BP1 foci, which slightly differed for cells irradiated in absence or presence of GNPs. At the nanoscale, Ripley’s distance frequency analysis of SMLM signal coordinate matrices also revealed relaxation of heterochromatin (H3K9me3) clusters upon IR. These changes were more prominent in presence of GNPs. The slight expansion of radiosensitive G2 cells correlated with mostly insignificant but systematic decrease in post-irradiation survival of GNP(+) cells. Interestingly, low GNP concentrations accelerated DSB repair kinetics; however, the numbers of persistent γH2AX/53BP1 repair foci were slightly increased in GNP(+) cells. (4) Conclusions: Low concentrations of 10-nm GNPs enhanced the G2/M cell cycle arrest and the proportion of radiosensitive G2 cells, but not the extent of DNA damage induction. GNPs also accelerated DSB repair kinetics and slightly increased presence of unrepaired γH2AX/53BP1 foci at 24 h PI. GNP-mediated cell effects correlated with slight radiosensitization of GNP(+) specimens, significant only for the highest radiation dose tested (4 Gy). Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures

Figure 1

14 pages, 2177 KiB

Open AccessArticle

Gold-Decorated Platinum and Palladium Nanoparticles as Modern Nanocomplexes to Improve the Effectiveness of Simulated Anticancer Proton Therapy

by Bartosz Klebowski, Malgorzata Stec, Joanna Depciuch, Adrianna Gałuszka, Anna Pajor-Swierzy, Jarek Baran and Magdalena Parlinska-Wojtan

Pharmaceutics 2021, 13(10), 1726; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101726 - 18 Oct 2021

Cited by 8 | Viewed by 2095

Abstract

Noble metal nanoparticles, such as gold (Au NPs), platinum (Pt NPs), or palladium (Pd NPs), due to their highly developed surface, stability, and radiosensitizing properties, can be applied to support proton therapy (PT) of cancer. In this paper, we investigated the potential of [...] Read more.

Noble metal nanoparticles, such as gold (Au NPs), platinum (Pt NPs), or palladium (Pd NPs), due to their highly developed surface, stability, and radiosensitizing properties, can be applied to support proton therapy (PT) of cancer. In this paper, we investigated the potential of bimetallic, c.a. 30 nm PtAu and PdAu nanocomplexes, synthesized by the green chemistry method and not used previously as radiosensitizers, to enhance the effect of colorectal cancer PT in vitro. The obtained nanomaterials were characterized by scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), UV-Vis spectroscopy, and zeta potential measurements. The effect of PtAu and PdAu NPs in PT was investigated on colon cancer cell lines (SW480, SW620, and HCT116), as well as normal colon epithelium cell line (FHC). These cells were cultured with both types of NPs and then irradiated by proton beam with a total dose of 15 Gy. The results of the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) test showed that the NPs-assisted PT resulted in a better anticancer effect than PT used alone; however, there was no significant difference in the radiosensitizing properties between tested nanocomplexes. The MTS results were further verified by defining the cell death as apoptosis (Annexin V binding assay). Furthermore, the data showed that such a treatment was more selective for cancer cells, as normal cell viability was only slightly affected. Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures

Figure 1

15 pages, 1960 KiB

Open AccessArticle

Integration of Transcriptomics and Metabolomics to Reveal the Molecular Mechanisms Underlying Rhodium Nanoparticles-Based Photodynamic Cancer Therapy

by Andres Machuca, Estefania Garcia-Calvo, Daniela S. Anunciação and Jose L. Luque-Garcia

Pharmaceutics 2021, 13(10), 1629; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101629 - 06 Oct 2021

Cited by 6 | Viewed by 1855

Abstract

Rhodium nanoparticles have recently been described as promising photosensitizers due to their low toxicity in the absence of near-infrared irradiation, but their high cytotoxicity when irradiated. Irradiation is usually carried out with a laser source, which allows the treatment to be localized in [...] Read more.

Rhodium nanoparticles have recently been described as promising photosensitizers due to their low toxicity in the absence of near-infrared irradiation, but their high cytotoxicity when irradiated. Irradiation is usually carried out with a laser source, which allows the treatment to be localized in a specific area, thus avoiding undesirable side effects on healthy tissues. In this study, a multi-omics approach based on the combination of microarray-based transcriptomics and mass spectrometry-based untargeted and targeted metabolomics has provided a global picture of the molecular mechanisms underlying the anti-tumoral effect of rhodium nanoparticle-based photodynamic therapy. The results have shown the ability of these nanoparticles to promote apoptosis by suppressing or promoting anti- and pro-apoptotic factors, respectively, and by affecting the energy machinery of tumor cells, mainly blocking the β-oxidation, which is reflected in the accumulation of free fatty acids and in the decrease in ATP, ADP and NAD+ levels. Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures

Graphical abstract

Review

Jump to: Research

29 pages, 4596 KiB

Open AccessEditor’s ChoiceReview

Recent Developments in Metallic Nanomaterials for Cancer Therapy, Diagnosing and Imaging Applications

by Dan Nicolae Păduraru, Daniel Ion, Adelina-Gabriela Niculescu, Florentina Mușat, Octavian Andronic, Alexandru Mihai Grumezescu and Alexandra Bolocan

Pharmaceutics 2022, 14(2), 435; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020435 - 17 Feb 2022

Cited by 51 | Viewed by 3874

Abstract

Cancer continues to represent a global health concern, imposing an ongoing need to research for better treatment alternatives. In this context, nanomedicine seems to be the solution to existing problems, bringing unprecedented results in various biomedical applications, including cancer therapy, diagnosing, and imaging. [...] Read more.

Cancer continues to represent a global health concern, imposing an ongoing need to research for better treatment alternatives. In this context, nanomedicine seems to be the solution to existing problems, bringing unprecedented results in various biomedical applications, including cancer therapy, diagnosing, and imaging. As numerous studies have uncovered the advantageous properties of various nanoscale metals, this review aims to present metal-based nanoparticles that are most frequently employed for cancer applications. This paper follows the description of relevant nanoparticles made of metals, metal derivatives, hybrids, and alloys, further discussing in more detail their potential applications in cancer management, ranging from the delivery of chemotherapeutics, vaccines, and genes to ablative hyperthermia therapies and theranostic platforms. Full article

(This article belongs to the Special Issue Metal-Based Nanoparticles: New Insights into Cancer Diagnosis and Therapy)

► Show Figures