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Implication of Nanoparticles in Cancer Therapy Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 15441

Special Issue Editors

Department of Life and Environmental Physics, Horia Hulubei National Institute of Physics and Nuclear Engineering, 077125 Magurele, Romania
Interests: radioresistant cancer cell biology; tumor cell radiosensitization; DNA damage signaling; mitochondria–nucleus communication; radiation-induced bystander effects; radiation response biomarkers; tumor microenvironment
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Guest Editor
“Horia Hulubei” National Insitute of Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Magurele, Romania
Interests: nanobiomaterials; drug delivery; cancer therapy; radiobiology; biocompatibility
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Clinically employed classical cancer therapies can cause unselective damage to healthy tissue. A growing body of research used nanotechnology to find strategies to overcome this disadvantage. Current research is focused on developing innovative therapies based on novel nanoparticles that enhance the therapeutic effect of chemotherapy and radiotherapy in order to reduce toxicity. Typical nanoparticles possess a wide range of physicochemical and biological properties including nano range size (less than 100 nm), a large surface area to volume ratio, specific structural properties, the ability to carry specific agents on their surface, the capacity to form stable interactions with ligands, the ability to overcome cellular or tissue barriers and to circulate in the blood for a long time, enhanced electrical conductivity, superparamagnetic behavior, the energy absorption, unique fluorescence properties. These features allow nanoparticles to facilitate drug delivery, multimodality treatment, and theranostics (combined therapy and diagnostic).

In this Special Issue, we expect contributions from a broad community of scientists working on developing new strategies based on nanoparticles to improve cancer chemotherapy/radiotherapy.

Dr. Diana Savu
Dr. Roxana Cristina Popescu
Guest Editors

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Keywords

  • nanotechnology
  • nanoparticles
  • nanocarriers
  • drug delivery
  • cancer therapy

Published Papers (7 papers)

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Research

18 pages, 10725 KiB  
Article
Nanoscale Iron-Based Metal–Organic Frameworks: Incorporation of Functionalized Drugs and Degradation in Biological Media
by Ioanna Christodoulou, Pengbo Lyu, Carla Vieira Soares, Gilles Patriarche, Christian Serre, Guillaume Maurin and Ruxandra Gref
Int. J. Mol. Sci. 2023, 24(4), 3362; https://doi.org/10.3390/ijms24043362 - 8 Feb 2023
Cited by 9 | Viewed by 1989
Abstract
Metal–organic frameworks (MOFs) attract growing interest in biomedical applications. Among thousands of MOF structures, the mesoporous iron(III) carboxylate MIL-100(Fe) (MIL stands for the Materials of Lavoisier Institute) is among the most studied MOF nanocarrier, owing to its high porosity, biodegradability, and lack of [...] Read more.
Metal–organic frameworks (MOFs) attract growing interest in biomedical applications. Among thousands of MOF structures, the mesoporous iron(III) carboxylate MIL-100(Fe) (MIL stands for the Materials of Lavoisier Institute) is among the most studied MOF nanocarrier, owing to its high porosity, biodegradability, and lack of toxicity. Nanosized MIL-100(Fe) particles (nanoMOFs) readily coordinate with drugs leading to unprecedented payloads and controlled release. Here, we show how the functional groups of the challenging anticancer drug prednisolone influence their interactions with the nanoMOFs and their release in various media. Molecular modeling enabled predicting the strength of interactions between prednisolone-bearing or not phosphate or sulfate moieties (PP and PS, respectively) and the oxo-trimer of MIL-100(Fe) as well as understanding the pore filling of MIL-100(Fe). Noticeably, PP showed the strongest interactions (drug loading up to 30 wt %, encapsulation efficiency > 98%) and slowed down the nanoMOFs’ degradation in simulated body fluid. This drug was shown to bind to the iron Lewis acid sites and was not displaced by other ions in the suspension media. On the contrary, PS was entrapped with lower efficiencies and was easily displaced by phosphates in the release media. Noticeably, the nanoMOFs maintained their size and faceted structures after drug loading and even after degradation in blood or serum after losing almost the totality of the constitutive trimesate ligands. Scanning electron microscopy with high annular dark field (STEM-HAADF) in conjunction with X-Ray energy-dispersive spectrometry (XEDS) was a powerful tool enabling the unraveling of the main elements to gain insights on the MOF structural evolution after drug loading and/or upon degradation. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research)
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14 pages, 4803 KiB  
Article
Nanoparticle-Mediated Drug Delivery of Doxorubicin Induces a Differentiated Clonogenic Inactivation in 3D Tumor Spheroids In Vitro
by Roxana Cristina Popescu, Verena Kopatz, Ecaterina Andronescu, Diana Iulia Savu and Wolfgang Doerr
Int. J. Mol. Sci. 2023, 24(3), 2198; https://doi.org/10.3390/ijms24032198 - 22 Jan 2023
Cited by 8 | Viewed by 2352
Abstract
Involvement of 3D tumor cell models in the in vitro biological testing of novel nanotechnology-based strategies for cancer management can provide in-depth information on the real behavior of tumor cells in complex biomimetic architectures. Here, we used polyethylene glycol-encapsulated iron oxide nanoparticles for [...] Read more.
Involvement of 3D tumor cell models in the in vitro biological testing of novel nanotechnology-based strategies for cancer management can provide in-depth information on the real behavior of tumor cells in complex biomimetic architectures. Here, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the controlled delivery of a doxorubicin chemotherapeutic substance (IONPDOX), and to enhance cytotoxicity of photon radiation therapy. The biological effects of nanoparticles and 150 kV X-rays were evaluated on both 2D and 3D cell models of normal human keratinocytes (HaCaT) and tumor cells—human cervical adenocarcinoma (HeLa) and human squamous carcinoma (FaDu)—through cell survival. In all 2D cell models, nanoparticles were similarly internalized in a peri-nuclear pattern, but resulted in different survival capabilities following radiation treatment. IONP on normal keratinocytes showed a protective effect, but a cytotoxic effect for cancer cells. In 3D tumor cell models, IONPDOX were able to penetrate the cell spheroids towards the hypoxic areas. However, IONPDOX and 150 kV X-rays led to a dose-modifying factor DMFSF=0.1 = 1.09 ± 0.1 (200 µg/mL IONPDOX) in HeLa spheroids, but to a radioprotective effect in FaDu spheroids. Results show that the proposed treatment is promising in the management of cervical adenocarcinoma. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research)
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16 pages, 2673 KiB  
Article
Synthetic Melanin Acts as Efficient Peptide Carrier in Cancer Vaccine Strategy
by Stefania Cuzzubbo, Benoit Roch, Guillaume Darrasse-Jèze, Benoit Hosten, Manon Leclercq, Nicolas Vignal, Claire Banissi, Eric Tartour and Antoine F. Carpentier
Int. J. Mol. Sci. 2022, 23(23), 14975; https://doi.org/10.3390/ijms232314975 - 29 Nov 2022
Cited by 2 | Viewed by 1894
Abstract
We previously reported that a novel peptide vaccine platform, based on synthetic melanin nanoaggregates, triggers strong cytotoxic immune responses and significantly suppresses tumor growth in mice. However, the mechanisms underlying such an efficacy remained poorly described. Herein, we investigated the role of dendritic [...] Read more.
We previously reported that a novel peptide vaccine platform, based on synthetic melanin nanoaggregates, triggers strong cytotoxic immune responses and significantly suppresses tumor growth in mice. However, the mechanisms underlying such an efficacy remained poorly described. Herein, we investigated the role of dendritic cells (DCs) in presenting the antigen embedded in the vaccine formulation, as well as the potential stimulatory effect of melanin upon these cells, in vitro by coculture experiments and ELISA/flow cytometry analysis. The vaccine efficiency was evaluated in FLT3-L−/− mice constitutively deficient in DC1, DC2, and pDCs, in Zbtb46DTR chimera mice deficient in DC1 and DC2, and in LangerinDTR mice deficient in dermal DC1 and Langerhans cells. We concluded that DCs, and especially migratory conventional type 1 dendritic cells, seem crucial for mounting the immune response after melanin-based vaccination. We also assessed the protective effect of L-DOPA melanin on peptides from enzymatic digestion, as well as the biodistribution of melanin–peptide nanoaggregates, after subcutaneous injection using [18F]MEL050 PET imaging in mice. L-DOPA melanin proved to act as an efficient carrier for peptides by fully protecting them from enzymatic degradation. L-DOPA melanin did not display any direct stimulatory effects on dendritic cells in vitro. Using PET imaging, we detected melanin–peptide nanoaggregates up to three weeks after subcutaneous injections within the secondary lymphoid tissues, which could explain the sustained immune response observed (up to 4 months) with this vaccine technology. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research)
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26 pages, 2741 KiB  
Article
EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters
by Damian Kaniowski, Justyna Suwara, Katarzyna Ebenryter-Olbińska, Agata Jakóbik-Kolon and Barbara Nawrot
Int. J. Mol. Sci. 2022, 23(23), 14793; https://doi.org/10.3390/ijms232314793 - 26 Nov 2022
Cited by 5 | Viewed by 1916
Abstract
New boron carriers with high boron content and targeted cancer-cell delivery are considered the first choice for boron neutron capture therapy (BNCT) for cancer treatment. Previously, we have shown that composites of antisense oligonucleotide and boron clusters are functional nanoparticles for the downregulation [...] Read more.
New boron carriers with high boron content and targeted cancer-cell delivery are considered the first choice for boron neutron capture therapy (BNCT) for cancer treatment. Previously, we have shown that composites of antisense oligonucleotide and boron clusters are functional nanoparticles for the downregulation of expression of epidermal growth factor receptor (EGFR) and can be loaded into EGFR-overexpressing cancer cells without a transfection factor. In this study, we hypothesize that free cellular uptake is mediated by binding and activation of the EGFR by boron clusters. Proteomic analysis of proteins pulled-down from various EGFR-overexpressing cancer cells using short oligonucleotide probes, conjugated to 1,2-dicarba-closo-dodecaborane (1,2-DCDDB, [C2B10H12]) and [(3,3′-Iron-1,2,1′,2′-dicarbollide)] (FESAN, [Fe(C2B9H11)2]), evidenced that boron cage binds to EGFR subdomains. Moreover, inductively coupled plasma mass spectrometry (ICP MS) and fluorescence microscopy analyses confirmed that FESANs-highly decorated B-ASOs were efficiently delivered and internalized by EGFR-overexpressing cells. Antisense reduction of EGFR in A431 and U87-MG cells resulted in decreased boron accumulation compared to control cells, indicating that cellular uptake of B-ASOs is related to EGFR-dependent internalization. The data obtained suggest that EGFR-mediated cellular uptake of B-ASO represents a novel strategy for cellular delivery of therapeutic nucleic acids (and possibly other medicines) conjugated to boron clusters. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research)
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15 pages, 5189 KiB  
Article
Immunization of Mice with Gold Nanoparticles Conjugated to Thermostable Cancer Antigens Prevents the Development of Xenografted Tumors
by Lev A. Dykman, Sergey A. Staroverov, Sergey V. Kozlov, Alexander S. Fomin, Daniil S. Chumakov, Konstantin P. Gabalov, Yevgeny S. Kozlov, Dmitry A. Soldatov and Nikolai G. Khlebtsov
Int. J. Mol. Sci. 2022, 23(22), 14313; https://doi.org/10.3390/ijms232214313 - 18 Nov 2022
Cited by 7 | Viewed by 1639
Abstract
Gold nanoparticles as part of vaccines greatly increase antigen stability, antigen accumulation in the lymph nodes, and antigen uptake by antigen-presenting cells. The use of such particles as part of anticancer vaccines based on heat shock proteins to increase vaccine effectiveness is timely. [...] Read more.
Gold nanoparticles as part of vaccines greatly increase antigen stability, antigen accumulation in the lymph nodes, and antigen uptake by antigen-presenting cells. The use of such particles as part of anticancer vaccines based on heat shock proteins to increase vaccine effectiveness is timely. We prepared and characterized nanoconjugates based on 15-nm gold nanoparticles and thermostable tumor antigens isolated from MH22a murine hepatoma cells. The whole-cell lysate of MH22a cells contained the main heat shock proteins. BALB/c mice were injected with the conjugates and then received transplants of MH22a cells. The highest titer was produced in mice immunized with the complex of gold nanoparticles + antigen with complete Freund’s adjuvant. The immunized mice showed no signs of tumor growth for 24 days. They also showed a decreased production of the INF-γ, IL-6, and IL-1 proinflammatory cytokines compared to the mice immunized through other schemes. This study is the first to show that it is possible in principle to use gold nanoparticles in combination with thermostable tumor antigens for antitumor vaccination. Antitumor vaccines based on thermostable tumor antigens can be largely improved by including gold nanoparticles as additional adjuvants. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research)
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16 pages, 2507 KiB  
Article
Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models
by Yang Kee Stella Man, Carmen Aguirre-Hernandez, Adrian Fernandez, Pilar Martin-Duque, Rebeca González-Pastor and Gunnel Halldén
Int. J. Mol. Sci. 2022, 23(16), 8884; https://doi.org/10.3390/ijms23168884 - 10 Aug 2022
Cited by 8 | Viewed by 2009
Abstract
Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, and kill adenocarcinoma cells with the added benefit of re-sensitising drug-resistant cells [...] Read more.
Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, and kill adenocarcinoma cells with the added benefit of re-sensitising drug-resistant cells in preclinical models. Further modifications are required to enable systemic delivery in patients due to the rapid hepatic elimination and neutralisation by blood factors and antibodies. Here, we show data that support the use of coating OAds with gold nanoparticles (AuNPs) as a possible new method of virus modification to help augment tumour uptake. The pre-incubation of cationic AuNPs with AdΔΔ, Ad-3∆-A20T and wild type adenovirus (Ad5wt) was performed prior to infection of prostate/pancreatic cancer cell lines (22Rv, PC3, Panc04.03, PT45) and a pancreatic stellate cell line (PS1). Levels of viral infection, replication and cell viability were quantified 24–72 h post-infection in the presence and absence of AuNPs. Viral spread was assessed in organotypic cultures. The presence of AuNPs significantly increased the uptake of Ad∆∆, Ad-3∆-A20T and Ad5wt in all the cell lines tested (ranging from 1.5-fold to 40-fold), compared to virus alone, with the greatest uptake observed in PS1, a usually adenovirus-resistant cell line. Pre-coating the AdΔΔ and Ad-3∆-A20T with AuNPs also increased viral replication, leading to enhanced cell killing, with maximal effect in the most virus-insensitive cells (from 1.4-fold to 5-fold). To conclude, the electrostatic association of virus with cationic agents provides a new avenue to increase the dose in tumour lesions and potentially protect the virus from detrimental blood factor binding. Such an approach warrants further investigation for clinical translation. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research)
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28 pages, 6156 KiB  
Article
Antibacterial Therapy by Ag+ Ions Complexed with Titan Yellow/Congo Red and Albumin during Anticancer Therapy of Urinary Bladder Cancer
by Anna Jagusiak, Tomasz Gosiewski, Dorota Romaniszyn, Małgorzata Lasota, Anna Wiśniewska, Katarzyna Chłopaś, Barbara Ostrowska, Izabela Kościk and Małgorzata Bulanda
Int. J. Mol. Sci. 2022, 23(1), 26; https://doi.org/10.3390/ijms23010026 - 21 Dec 2021
Cited by 5 | Viewed by 2689
Abstract
According to the World Health Organization report, the increasing antibiotic resistance of microorganisms is one of the biggest global health problems. The percentage of bacterial strains showing multidrug resistance (MDR) to commonly used antibiotics is growing rapidly. Therefore, the search for alternative solutions [...] Read more.
According to the World Health Organization report, the increasing antibiotic resistance of microorganisms is one of the biggest global health problems. The percentage of bacterial strains showing multidrug resistance (MDR) to commonly used antibiotics is growing rapidly. Therefore, the search for alternative solutions to antibiotic therapy has become critical to combat this phenomenon. It is especially important as frequent and recurring infections can cause cancer. One example of this phenomenon is urinary tract infections that can contribute to the development of human urinary bladder carcinoma. This tumor is one of the most common malignant neoplasms in humans. It occurs almost three times more often in men than in women, and in terms of the number of cases, it is the fifth malignant neoplasm after prostate, lung, colon, and stomach cancer. The risk of developing the disease increases with age. Despite the improvement of its treatment methods, the current outcome in the advanced stages of this tumor is not satisfactory. Hence, there is an urgent need to introduce innovative solutions that will prove effective even in the advanced stage of the disease. In our study, a nanosystem based on ionic silver (Ag+) bound to a carrier—Titan yellow (TY) was analyzed. The possibility of binding the thus formed TY-Ag system to Congo red (CR) and albumin (BSA) was determined. TY-Ag binding to CR provides for better nanosystem solubility and enables its targeted intracellular transport and binding to immune complexes. The binding of TY-Ag or CR-TY-Ag to albumin also protects the system against the uncontrolled release of silver ions. It will also allow the delivery of silver in a targeted manner directly to the desired site in the case of intravenous administration of such a system. In this study, the MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values of the TY-Ag or BSA-TY-Ag systems were determined in two reference strains (Escherichia coli and Staphylococcus aureus). The paper presents nanosystems with a size of about 40–50 nm, with an intense antibacterial effect obtained at concentrations of 0.019 mM. We have also discovered that TY-Ag free or complexed with BSA (with a minimal Ag+ dose of 15–20 μM) inhibited cancer cells proliferation. TY-Ag complex diminished migration and effectively inhibited the T24 cell viability and induced apoptosis. On the basis of the obtained results, it has been shown that the presented systems may have anti-inflammatory and antitumor properties at the same time. TY-Ag or BSA-TY-Ag are new potential drugs and may become in future important therapeutic compounds in human urinary bladder carcinoma treatment and/or potent antimicrobial factors as an alternative to antibiotics. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research)
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