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Nanomaterials for Cancer Diagnosis and Therapy

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Nanochemistry".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 81838

Special Issue Editors


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Guest Editor
Materials and Aeroespatial Production Department, Polymer Materials Research Group, 28040 Madrid, Spain
Interests: nanomedicine; stimuli-responsive drug nanocarriers; nano-oncology; nanomotors for clinical diagnosis; nanomaterials; development of targeting moieties based on synthetic small molecules for antitumoral therapy; protein encapsulation; polymeric nanocapsules for protein delivery in medicine; nanorobots
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, 08193 Barcelona, Spain
2. Departament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain
Interests: nanomedicine; nanoparticles; nanomaterials; drug delivery; bioimaging; nanostructured coordination polymers for biomedical applications; synthesis and characterization of hybrid nanoparticles; polymeric nanoparticles, novel strategies for cancer therapy; theranostics

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Guest Editor
Department of Life Sciences, Nano4Health Unit, Nanomedicine Group, International Iberian Nanotechnology Laboratory (INL), Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal
Interests: nanomedicine; liposomes; gene transfection; microfluidics; drug delivery; stimuli-responsive nanodevices
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanotechnology has become a powerful weapon in the fight against cancer. The development of precisely engineered nanoparticles able to overcome biological barriers, specifically recognize and destroy a single type of cancer cell, and accumulate preferentially in tumours, offers a new and potent arsenal to oncologists. Inorganic and organic (or polymeric) nanoparticles have been widely explored for therapeutic and diagnostic applications in cancer treatment. Normally, single nanoparticles are often used and functionalized with organic or polymeric ligands to improve their stability, biocompatibility, and functionality. While individual nanoparticles are no doubt exciting, ensemble of interacting nanoparticles can exhibit a rich variety of novel and extremely useful collective properties that can be radically different from their individual characteristics. These new synergistic properties are originated from coupling interactions in the ensemble of nanoparticles. It is, therefore, expected that the ability to design hybrid structures with tailored spatial arrangements of nanoparticles may facilitate the utilization of nanoparticles in biomedical applications. Recent advances in nanomedicine raise exciting possibilities for future nanoparticle applications in personalized cancer therapy, and new strategies for building hybrid nanostructures are offering interesting platforms, such as effective multimodality cancer imaging (i.e., photothermal, photoacoustic, and magnetic resonance imaging) and combinational cancer therapy (i.e., photothermal ablation of tumors, photodynamic therapy, and targeted delivery-based chemotherapy).

In this Special Issue, we invite investigators to contribute original research articles as well as review articles that are related to the application of hybrid nanoparticles as multifunctional platforms in the treatment and early diagnosis of cancer. We are particularly interested in research directed toward improving the effectivity and selectivity properties of different nanoparticles for treatment or bioimaging purposes. Potential topics include, but are not limited to:

  • Theranostic nanoparticles for cancer treatment
  • Nanoparticles as contrast agents for bioimaging
  • Nanoparticles as biosensors
  • Novel therapies based on nanomaterials for cancer treatment and diagnosis
  • Clinical studies and therapeutic and diagnostic efficacy of anti-cancer nanoparticles
  • Biocompatibility and toxicity studies of nanoparticles for cancer treatment.

Dr. Alejandro Baeza
Dr. Fernando Novio
Dr. Juan Luis Paris
Guest Editors

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Keywords

  • Nanotechnology
  • hybrid nanoparticles
  • theranostics
  • cancer therapy
  • biocompatibility
  • Imaging
  • drug delivery
  • clinical trials
  • toxicology
  • detection
  • screening
  • targeting moieties

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Published Papers (15 papers)

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Research

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17 pages, 3477 KiB  
Article
In Vitro Evaluation of Lipopolyplexes for Gene Transfection: Comparing 2D, 3D and Microdroplet-Enabled Cell Culture
by Juan L. Paris, Filipe Coelho, Alexandra Teixeira, Lorena Diéguez, Bruno F. B. Silva and Sara Abalde-Cela
Molecules 2020, 25(14), 3277; https://doi.org/10.3390/molecules25143277 - 18 Jul 2020
Cited by 8 | Viewed by 4531
Abstract
Complexes combining nucleic acids with lipids and polymers (lipopolyplexes) show great promise for gene therapy since they enable compositional, physical and functional versatility to be optimized for therapeutic efficiency. When developing lipopolyplexes for gene delivery, one of the first evaluations performed is an [...] Read more.
Complexes combining nucleic acids with lipids and polymers (lipopolyplexes) show great promise for gene therapy since they enable compositional, physical and functional versatility to be optimized for therapeutic efficiency. When developing lipopolyplexes for gene delivery, one of the first evaluations performed is an in vitro transfection efficiency experiment. Many different in vitro models can be used, and the effect of the model on the experiment outcome has not been thoroughly studied. The objective of this work was to compare the insights obtained from three different in vitro models, as well as the potential limitations associated with each of them. We have prepared a series of lipopolyplex formulations with three different cationic polymers (poly-l-lysine, bioreducible poly-l-lysine and polyethyleneimine), and assessed their in vitro biological performance in 2D monolayer cell culture, 3D spheroid culture and microdroplet-based single-cell culture. Lipopolyplexes from different polymers presented varying degrees of transfection efficiency in all models. The best-performing formulation in 2D culture was the polyethyleneimine lipopolyplex, while lipoplexes prepared with bioreducible poly-l-lysine were the only ones achieving any transfection in microdroplet-enabled cell culture. None of the prepared formulations achieved significant gene transfection in 3D culture. All of the prepared formulations were well tolerated by cells in 2D culture, while at least one formulation (poly-l-lysine polyplex) delayed 3D spheroid growth. These results highlight the need for selecting the appropriate in vitro model depending on the intended application. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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20 pages, 4924 KiB  
Article
Silica Coated Iron/Iron Oxide Nanoparticles as a Nano-Platform for T2 Weighted Magnetic Resonance Imaging
by Paul Mathieu, Yannick Coppel, Marc Respaud, Quyen T. Nguyen, Sébastien Boutry, Sophie Laurent, Dimitri Stanicki, Céline Henoumont, Fernando Novio, Julia Lorenzo, David Montpeyó and Catherine Amiens
Molecules 2019, 24(24), 4629; https://doi.org/10.3390/molecules24244629 - 17 Dec 2019
Cited by 23 | Viewed by 5049
Abstract
The growing concern over the toxicity of Gd-based contrast agents used in magnetic resonance imaging (MRI) motivates the search for less toxic and more effective alternatives. Among these alternatives, iron–iron oxide (Fe@FeOx) core-shell architectures have been long recognized as promising MRI contrast agents [...] Read more.
The growing concern over the toxicity of Gd-based contrast agents used in magnetic resonance imaging (MRI) motivates the search for less toxic and more effective alternatives. Among these alternatives, iron–iron oxide (Fe@FeOx) core-shell architectures have been long recognized as promising MRI contrast agents while limited information on their engineering is available. Here we report the synthesis of 10 nm large Fe@FeOx nanoparticles, their coating with a 11 nm thick layer of dense silica and functionalization by 5 kDa PEG chains to improve their biocompatibility. The nanomaterials obtained have been characterized by a set of complementary techniques such as infra-red and nuclear magnetic resonance spectroscopies, transmission electron microscopy, dynamic light scattering and zetametry, and magnetometry. They display hydrodynamic diameters in the 100 nm range, zetapotential values around −30 mV, and magnetization values higher than the reference contrast agent RESOVIST®. They display no cytotoxicity against 1BR3G and HCT116 cell lines and no hemolytic activity against human red blood cells. Their nuclear magnetic relaxation dispersion (NMRD) profiles are typical for nanomaterials of this size and magnetization. They display high r2 relaxivity values and low r1 leading to enhanced r2/r1 ratios in comparison with RESOVIST®. All these data make them promising contrast agents to detect early stage tumors. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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19 pages, 5032 KiB  
Article
Development of 11-DGA-3-O-Gal-Modified Cantharidin Liposomes for Treatment of Hepatocellular Carcinoma
by Lili Zhou, Manshu Zou, Kun Zhu, Shuangcheng Ning and Xinhua Xia
Molecules 2019, 24(17), 3080; https://doi.org/10.3390/molecules24173080 - 24 Aug 2019
Cited by 19 | Viewed by 3551
Abstract
Background: Liver cancer is a common malignant tumor worldwide, and its morbidity and mortality increase each year. The disease has a short course and high mortality, making it a serious threat to human health. Purpose: The objective of this study was to create [...] Read more.
Background: Liver cancer is a common malignant tumor worldwide, and its morbidity and mortality increase each year. The disease has a short course and high mortality, making it a serious threat to human health. Purpose: The objective of this study was to create novel liver-targeting nanoliposomes to encapsulate cantharidin (CTD) as a potential treatment for hepatic carcinoma. Methods: 3-Galactosidase-30-stearyl deoxyglycyrrhetinic acid (11-DGA-3-O-Gal)-modified liposomes (11-DGA-3-O-Gal-CTD-lip) for the liver-targeted delivery of CTD were prepared via the film-dispersion method and characterized. In vitro analyses of the effects on cellular cytotoxicity, cell migration, cell cycle, and cell apoptosis were carried out and an in vivo pharmacokinetics study and tissue distribution analysis were performed. Results: Compared with unmodified liposomes (CTD-lip), 11-DGA-3-O-Gal-CTD-lip showed higher cytotoxicity and increased the inhibition of HepG2 cell migration, but they did not increase the apoptotic rate of cells. The inhibition mechanism of 11-DGA-3-O-Gal-CTD-lip on hepatocellular carcinoma was partly through cell cycle arrest at the S phase. Analysis of pharmacokinetic parameters indicated that 11-DGA-3-O-Gal-CTD-lip were eliminated more rapidly than CTD-lip. Regarding tissue distribution, the targeting efficiency of 11-DGA-3-O-Gal-CTD-lip to the liver was (41.15 ± 3.28)%, relative targeting efficiency was (1.53 ± 0.31)%, relative uptake rate was( 1.69 ± 0.37)%, and peak concentration ratio was (2.68 ± 0.12)%. Conclusion: 11-DGA-3-O-Gal-CTD-lip represent a promising nanocarrier for the liver-targeted delivery of antitumor drugs to treat hepatocellular carcinoma. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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16 pages, 1623 KiB  
Article
Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia
by Noureldien H. E. Darwish, Thangirala Sudha, Kavitha Godugu, Dhruba J. Bharali, Osama Elbaz, Hasan A. Abd El-ghaffar, Emad Azmy, Nahla Anber and Shaker A. Mousa
Molecules 2019, 24(11), 2103; https://doi.org/10.3390/molecules24112103 - 3 Jun 2019
Cited by 50 | Viewed by 5981
Abstract
The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been [...] Read more.
The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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16 pages, 4599 KiB  
Article
Diamond Nanoparticles Downregulate Expression of CycD and CycE in Glioma Cells
by Marta Grodzik, Jaroslaw Szczepaniak, Barbara Strojny-Cieslak, Anna Hotowy, Mateusz Wierzbicki, Slawomir Jaworski, Marta Kutwin, Emilia Soltan, Tomasz Mandat, Aneta Lewicka and Andre Chwalibog
Molecules 2019, 24(8), 1549; https://doi.org/10.3390/molecules24081549 - 19 Apr 2019
Cited by 6 | Viewed by 4248
Abstract
Our previous studies have shown that diamond nanoparticles (NDs) exhibited antiangiogenic and proapoptotic properties in vitro in glioblastoma multiforme (GBM) cells and in tumors in vivo. Moreover, NDs inhibited adhesion, leading to the suppression of migration and invasion of GBM. In the present [...] Read more.
Our previous studies have shown that diamond nanoparticles (NDs) exhibited antiangiogenic and proapoptotic properties in vitro in glioblastoma multiforme (GBM) cells and in tumors in vivo. Moreover, NDs inhibited adhesion, leading to the suppression of migration and invasion of GBM. In the present study, we hypothesized that the NDs might also inhibit proliferation and cell cycle in glioma cells. Experiments were performed in vitro with the U87 and U118 lines of GBM cells, and for comparison, the Hs5 line of stromal cells (normal cells) after 24 h and 72 h of treatment. The analyses included cell morphology, cell death, viability, and cell cycle analysis, double timing assay, and gene expression (Rb, E2F1, CycA, CycB, CycD, CycE, PTEN, Ki-67). After 72 h of ND treatment, the expression level of Rb, CycD, and CycE in the U118 cells, and E2F1, CycD, and CycE in the U87 cells were significantly lower in comparison to those in the control group. We observed that decreased expression of cyclins inhibited the G1/S phase transition, arresting the cell cycle in the G0/G1 phase in glioma cells. The NDs did not affect the cell cycle as well as PTEN and Ki-67 expression in normal cells (Hs5), although it can be assumed that the NDs reduced proliferation and altered the cell cycle in fast dividing cells. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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14 pages, 2636 KiB  
Article
Size-Dependent Biological Effects of Quercetin Nanocrystals
by Qian Liu, Xi Yang, Jianxu Sun, Fanglin Yu, Hui Zhang, Jing Gao and Aiping Zheng
Molecules 2019, 24(7), 1438; https://doi.org/10.3390/molecules24071438 - 11 Apr 2019
Cited by 19 | Viewed by 3890
Abstract
Quercetin (QE) is an attractive natural compound for cancer prevention due to its beneficial anti-oxidative and anti-proliferative effects. However, QE is poorly soluble in water and slightly soluble in oil, which results in its low oral bioavailability and limits its application in the [...] Read more.
Quercetin (QE) is an attractive natural compound for cancer prevention due to its beneficial anti-oxidative and anti-proliferative effects. However, QE is poorly soluble in water and slightly soluble in oil, which results in its low oral bioavailability and limits its application in the clinic. The aim of this study was to prepare QE nanocrystals (QE-NCs) with improved solubility and high drug loading, furthermore, the size-dependent anti-cancer effects of QE-NCs were studied. We prepared QE-NCs with three different particle sizes by wet milling, then, cell proliferation, migration and invasion were studied in A549 cells. The QE-NCs had antitumor effects in a dose- and size-dependent manner. Compared with the large particles, the small particles had a strong inhibitory impact on cell biological effects (p < 0.05 or p < 0.01). Moreover, Western blot assay indicated that QE-NCs may inhibit the migration and invasion of A549 cells by inhibiting the STAT3 signaling pathway, and the particle size may have an effect on this process. In this study, it was proven that NCs could dramatically enhance the anticancer efficacy of QE at the cellular level. In addition, particle size had a considerable influence on the dissolution behavior and antitumor effects of NCs. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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11 pages, 3804 KiB  
Article
Nanoformulation of a Novel Pyrano[2,3-c] Pyrazole Heterocyclic Compound AMDPC Exhibits Anti-Cancer Activity via Blocking the Cell Cycle through a P53-Independent Pathway
by Xuanrong Sun, Longchao Zhang, Mengshi Gao, Xiangjie Que, Chenfeng Zhou, Dabu Zhu and Yue Cai
Molecules 2019, 24(3), 624; https://doi.org/10.3390/molecules24030624 - 11 Feb 2019
Cited by 28 | Viewed by 3529
Abstract
Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated [...] Read more.
Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated as AMDPC). The IC50 of AMDPC against Bcap-37 breast cancer cells was 46.52 μg/mL. Then the hydrophobic AMDPC was encapsulated in PEG-PLGA block copolymers, and then self-assembled as polymeric micelle (mPEG-PLGA/AMDPC) to improve both physiochemical and release profiles. The effect of mPEG-PLGA/AMDPC on BCAP-37 cancer cells showed similar anti-tumor effects as AMDPC. Furthermore, the anti-tumor mechanism of mPEG-PLGA/AMDPC was investigated, which can probably be attributed to stimulating the expression of P21 gene and therefore protein production on BCAP-37 cells, and then blocked the cell cycle through the P53-independent pathway both in S phase and G2 phase. Thus, mPEG-PLGA/AMDPC is a promising therapeutic agent for cancer treatment, and further in vivo studies will be developed. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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Review

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39 pages, 3857 KiB  
Review
Lipid-Nucleic Acid Complexes: Physicochemical Aspects and Prospects for Cancer Treatment
by Ricardo Gaspar, Filipe Coelho and Bruno F. B. Silva
Molecules 2020, 25(21), 5006; https://doi.org/10.3390/molecules25215006 - 28 Oct 2020
Cited by 38 | Viewed by 6035
Abstract
Cancer is an extremely complex disease, typically caused by mutations in cancer-critical genes. By delivering therapeutic nucleic acids (NAs) to patients, gene therapy offers the possibility to supplement, repair or silence such faulty genes or to stimulate their immune system to fight the [...] Read more.
Cancer is an extremely complex disease, typically caused by mutations in cancer-critical genes. By delivering therapeutic nucleic acids (NAs) to patients, gene therapy offers the possibility to supplement, repair or silence such faulty genes or to stimulate their immune system to fight the disease. While the challenges of gene therapy for cancer are significant, the latter approach (a type of immunotherapy) starts showing promising results in early-stage clinical trials. One important advantage of NA-based cancer therapies over synthetic drugs and protein treatments is the prospect of a more universal approach to designing therapies. Designing NAs with different sequences, for different targets, can be achieved by using the same technologies. This versatility and scalability of NA drug design and production on demand open the way for more efficient, affordable and personalized cancer treatments in the future. However, the delivery of exogenous therapeutic NAs into the patients’ targeted cells is also challenging. Membrane-type lipids exhibiting permanent or transient cationic character have been shown to associate with NAs (anionic), forming nanosized lipid-NA complexes. These complexes form a wide variety of nanostructures, depending on the global formulation composition and properties of the lipids and NAs. Importantly, these different lipid-NA nanostructures interact with cells via different mechanisms and their therapeutic potential can be optimized to promising levels in vitro. The complexes are also highly customizable in terms of surface charge and functionalization to allow a wide range of targeting and smart-release properties. Most importantly, these synthetic particles offer possibilities for scaling-up and affordability for the population at large. Hence, the versatility and scalability of these particles seem ideal to accommodate the versatility that NA therapies offer. While in vivo efficiency of lipid-NA complexes is still poor in most cases, the advances achieved in the last three decades are significant and very recently a lipid-based gene therapy medicine was approved for the first time (for treatment of hereditary transthyretin amyloidosis). Although the path to achieve efficient NA-delivery in cancer therapy is still long and tenuous, these advances set a new hope for more treatments in the future. In this review, we attempt to cover the most important biophysical and physicochemical aspects of non-viral lipid-based gene therapy formulations, with a perspective on future cancer treatments in mind. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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16 pages, 1977 KiB  
Review
Design of Targeted Nanostructured Coordination Polymers (NCPs) for Cancer Therapy
by Fernando Novio
Molecules 2020, 25(15), 3449; https://doi.org/10.3390/molecules25153449 - 29 Jul 2020
Cited by 16 | Viewed by 3683
Abstract
Conventional cancer chemotherapy presents notable drug side effects due to non-selective action of the chemotherapeutics to normal cells. Nanoparticles decorated with receptor-specific ligands on the surface have shown an important role in improving site-selective binding, retention, and drug delivery to the cancer cells. [...] Read more.
Conventional cancer chemotherapy presents notable drug side effects due to non-selective action of the chemotherapeutics to normal cells. Nanoparticles decorated with receptor-specific ligands on the surface have shown an important role in improving site-selective binding, retention, and drug delivery to the cancer cells. This review summarizes the recent reported achievements using nanostructured coordination polymers (NCPs) with active targeting properties for cancer treatment in vitro and in vivo. Despite the controversy surrounding the effectivity of active targeting nanoparticles, several studies suggest that active targeting nanoparticles notably increase the selectivity and the cytotoxic effect in tumoral cells over the conventional anticancer drugs and non-targeted nanoparticle platform, which enhances drug efficacy and safety. In most cases, the nanocarriers have been endowed with remarkable capabilities such as stimuli-responsive properties, targeting abilities, or the possibility to be monitored by imaging techniques. Unfortunately, the lack of preclinical studies impedes the evaluation of these unique and promising findings for the translation of NCPs into clinical trials. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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30 pages, 5290 KiB  
Review
Magnetic Hyperthermia for Cancer Treatment: Main Parameters Affecting the Outcome of In Vitro and In Vivo Studies
by Vânia Vilas-Boas, Félix Carvalho and Begoña Espiña
Molecules 2020, 25(12), 2874; https://doi.org/10.3390/molecules25122874 - 22 Jun 2020
Cited by 79 | Viewed by 7654
Abstract
Magnetic hyperthermia (MHT) is being investigated as a cancer treatment since the 1950s. Recent advancements in the field of nanotechnology have resulted in a notable increase in the number of MHT studies. Most of these studies explore MHT as a stand-alone treatment or [...] Read more.
Magnetic hyperthermia (MHT) is being investigated as a cancer treatment since the 1950s. Recent advancements in the field of nanotechnology have resulted in a notable increase in the number of MHT studies. Most of these studies explore MHT as a stand-alone treatment or as an adjuvant therapy in a preclinical context. However, despite all the scientific effort, only a minority of the MHT-devoted nanomaterials and approaches made it to clinical context. The outcome of an MHT experiment is largely influenced by a number of variables that should be considered when setting up new MHT studies. This review highlights and discusses the main parameters affecting the outcome of preclinical MHT, aiming to provide adequate assistance in the design of new, more efficient MHT studies. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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21 pages, 1954 KiB  
Review
Tumor Targeted Nanocarriers for Immunotherapy
by Alejandro Baeza
Molecules 2020, 25(7), 1508; https://doi.org/10.3390/molecules25071508 - 26 Mar 2020
Cited by 28 | Viewed by 5120
Abstract
The paramount discovery of passive accumulation of nanoparticles in tumoral tissues triggered the development of a wide number of different nanoparticles capable of transporting therapeutic agents to tumoral tissues in a controlled and selective way. These nanocarriers have been endowed with important capacities [...] Read more.
The paramount discovery of passive accumulation of nanoparticles in tumoral tissues triggered the development of a wide number of different nanoparticles capable of transporting therapeutic agents to tumoral tissues in a controlled and selective way. These nanocarriers have been endowed with important capacities such as stimuli-responsive properties, targeting abilities, or the capacity to be monitored by imaging techniques. However, after decades of intense research efforts, only a few nanomedicines have reached the market. The reasons for this disappointing outcome are varied, from the high tumor-type dependence of enhanced permeation and retention (EPR) effect to the poor penetration capacity of nanocarriers within the cancerous tissue, among others. The rapid nanoparticle clearance by immune cells, considered another important barrier, which compromises the efficacy of nanomedicines, would become an important ally in the fight against cancer. In the last years, the fine-tuned ability of immune cells to recognize and engulf nanoparticles have been exploited to deliver immunoregulating agents to specific immune cell populations selectively. In this work, the recent advances carried out in the development of nanocarriers capable of operating with immune and tumoral cells in order to orchestrate an efficient antitumoral response will be presented. The combination of nanoparticles and immunotherapy would deliver powerful weapons to the clinicians that offer safer and more efficient antitumoral treatments for the patients. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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25 pages, 897 KiB  
Review
Cell-Based Nanoparticles Delivery Systems for Targeted Cancer Therapy: Lessons from Anti-Angiogenesis Treatments
by Paz de la Torre, María Jesús Pérez-Lorenzo, Álvaro Alcázar-Garrido and Ana I. Flores
Molecules 2020, 25(3), 715; https://doi.org/10.3390/molecules25030715 - 7 Feb 2020
Cited by 66 | Viewed by 7509
Abstract
The main strategy of cancer treatment has focused on attacking the tumor cells. Some cancers initially responsive to chemotherapy become treatment-resistant. Another strategy is to block the formation of tumor vessels. However, tumors also become resistant to anti-angiogenic treatments, mostly due to other [...] Read more.
The main strategy of cancer treatment has focused on attacking the tumor cells. Some cancers initially responsive to chemotherapy become treatment-resistant. Another strategy is to block the formation of tumor vessels. However, tumors also become resistant to anti-angiogenic treatments, mostly due to other cells and factors present in the tumor microenvironment, and hypoxia in the central part of the tumor. The need for new cancer therapies is significant. The use of nanoparticle-based therapy will improve therapeutic efficacy and targeting, while reducing toxicity. However, due to inefficient accumulation in tumor sites, clearance by reticuloendothelial organs and toxicity, internalization or conjugation of drug-loaded nanoparticles (NPs) into mesenchymal stem cells (MSCs) can increase efficacy by actively delivering them into the tumor microenvironment. Nanoengineering MSCs with drug-loaded NPs can increase the drug payload delivered to tumor sites due to the migratory and homing abilities of MSCs. However, MSCs have some disadvantages, and exosomes and membranes from different cell types can be used to transport drug-loaded NPs actively to tumors. This review gives an overview of different cancer approaches, with a focus on hypoxia and the emergence of NPs as drug-delivery systems and MSCs as cellular vehicles for targeted delivery due to their tumor-homing potential. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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21 pages, 820 KiB  
Review
Nanobiomaterials Used in Cancer Therapy: An Up-To-Date Overview
by Iulia Ioana Lungu, Alexandru Mihai Grumezescu, Adrian Volceanov and Ecaterina Andronescu
Molecules 2019, 24(19), 3547; https://doi.org/10.3390/molecules24193547 - 30 Sep 2019
Cited by 90 | Viewed by 6549
Abstract
The disadvantages that come with traditional cancer treatments, such as chemotherapy and radiotherapy, generated a research shift toward nanotechnology. However, even with the important advancements regarding cancer therapy, there are still serious stepping stones that need to be addressed. The use of both [...] Read more.
The disadvantages that come with traditional cancer treatments, such as chemotherapy and radiotherapy, generated a research shift toward nanotechnology. However, even with the important advancements regarding cancer therapy, there are still serious stepping stones that need to be addressed. The use of both nanotechnology and nanomedicine has generated significant improvements in nano-sized materials development and their use as therapeutic, diagnosis, and imaging agents. The biological barriers that come from the healthy body, as well from the tumorous sites, are important parameters that need to be taken into consideration when designing drug delivery systems. There are several aspects of extreme importance such as the tumor microenvironment and vasculature, the reticuloendothelial system, the blood–brain barrier, the blood–tumor barrier, and the renal system. In order to achieve an effective system for cancer therapy, several characteristics of the nanoparticles have been outlined. Moreover, this review has also focused on the different types of nanoparticles that have been studied over the years as potential candidates for cancer therapy. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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34 pages, 1701 KiB  
Review
Nano-and Micromotors Designed for Cancer Therapy
by Luisa Sonntag, Juliane Simmchen and Veronika Magdanz
Molecules 2019, 24(18), 3410; https://doi.org/10.3390/molecules24183410 - 19 Sep 2019
Cited by 55 | Viewed by 8103
Abstract
Research on nano- and micromotors has evolved into a frequently cited research area with innovative technology envisioned for one of current humanities’ most deadly problems: cancer. The development of cancer targeting drug delivery strategies involving nano-and micromotors has been a vibrant field of [...] Read more.
Research on nano- and micromotors has evolved into a frequently cited research area with innovative technology envisioned for one of current humanities’ most deadly problems: cancer. The development of cancer targeting drug delivery strategies involving nano-and micromotors has been a vibrant field of study over the past few years. This review aims at categorizing recent significant results, classifying them according to the employed propulsion mechanisms starting from chemically driven micromotors, to field driven and biohybrid approaches. In concluding remarks of section 2, we give an insight into shape changing micromotors that are envisioned to have a significant contribution. Finally, we critically discuss which important aspects still have to be addressed and which challenges still lie ahead of us. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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12 pages, 685 KiB  
Review
Simultaneous Photodiagnosis and Photodynamic Treatment of Metastatic Melanoma
by Channay Naidoo, Cherie Ann Kruger and Heidi Abrahamse
Molecules 2019, 24(17), 3153; https://doi.org/10.3390/molecules24173153 - 29 Aug 2019
Cited by 35 | Viewed by 4745
Abstract
Metastatic melanoma (MM) has a poor prognosis and is attributed to late diagnoses only when metastases has already occurred. Thus, early diagnosis is crucial to improve its overall treatment efficacy. The standard diagnostic tools for MM are incisional biopsies and/or fine needle aspiration [...] Read more.
Metastatic melanoma (MM) has a poor prognosis and is attributed to late diagnoses only when metastases has already occurred. Thus, early diagnosis is crucial to improve its overall treatment efficacy. The standard diagnostic tools for MM are incisional biopsies and/or fine needle aspiration biopsies, while standard treatments involve surgery, chemotherapy, or irradiation therapy. The combination of photodynamic diagnosis (PDD) and therapy (PDT) utilizes a photosensitizer (PS) that, when excited by light of a low wavelength, can be used for fluorescent non-destructive diagnosis. However, when the same PS is activated at a higher wavelength of light, it can be cytotoxic and induce tumor destruction. This paper focuses on PS drugs that have been used for PDD as well as PDT treatment of MM. Furthermore, it emphasizes the need for continued investigation into enhanced PS delivery via active biomarkers and passive nanoparticle systems. This should improve PS drug absorption in MM cells and increase effectiveness of combinative photodynamic methods for the enhanced diagnosis and treatment of MM can become a reality. Full article
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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