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Nanomaterials for Pro-/Anti-Angiogenic Therapies

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

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 69298

Special Issue Editor

Head of Nano Hybrid BioInterfaces Lab (NHBIL), Department of Chemical Sciences, University of Catania, Catania, Italy
Interests: physical chemistry of surfaces; soft wet hybrid interfaces; biomaterials; sensors; nano- biointerfaces
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Angiogenesis, the functional formation of new blood vessels from existing vasculature, is also known as one of the hallmarks of diseases, playing a pivotal role in age-related pathologies, arthritis, ischemic heart disease, tumorigenesis and metastasis. Angiogenesis is mediated through several growth factors and angiopoietic hormones. It is well established that impairment in the angiogenesis process can result in various fatal conditions. Among different types of therapeutic strategies, nanotechnology is emerging as a new approach for the treatment of angiogenesis-related diseases. Nanoparticles with tunable size, shape and surface tailoring have been exploited to achieve effective tumor vascular targeting as well as new promising perspectives in the theranostic field of regenerative nanomedicine. As found in several in vitro and in vivo experiments, nanomaterials are efficient in depriving tumor cells from nutrients and oxygen by inhibiting angiogenesis. On the other hand, methods of targeted angiogenesis in the ischemic areas based on functionalized nanoparticles would be very useful as a novel and challenging therapeutic measure.

In this issue, a particular focus is put on these subjects. We welcome articles with a strong physicochemical and materials science focus, dealing with the topics of surface modification of nanomaterials for tunable interaction at the biointerfaces in all aspects related with promoting or depriving angiogenesis processes in pathological conditions.

Prof. Dr. Cristina Satriano
Guest Editor

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Keywords

  • angiogenesis
  • nanoparticles
  • hybrid nanomaterials
  • soft matter
  • nanomedicine
  • theranostics
  • surface functionalization
  • biointerfaces
  • growth factors
  • peptides

Published Papers (13 papers)

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Research

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23 pages, 3854 KiB  
Article
Anti-Angiogenic and Anti-Proliferative Graphene Oxide Nanosheets for Tumor Cell Therapy
by Valeria Verde, Anna Longo, Lorena Maria Cucci, Vanessa Sanfilippo, Antonio Magrì, Cristina Satriano, Carmelina Daniela Anfuso, Gabriella Lupo and Diego La Mendola
Int. J. Mol. Sci. 2020, 21(15), 5571; https://doi.org/10.3390/ijms21155571 - 04 Aug 2020
Cited by 17 | Viewed by 2986
Abstract
Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the [...] Read more.
Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)4-NH2 peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC). The anti-angiogenic response of the two cellular models of angiogenesis, namely endothelial and prostate cancer cells, was scrutinized by prostaglandin E2 (PGE2) release and wound scratch assays, to correlate the activation of inflammatory response upon the cell treatments with the GO@peptide nanocomposites to the cell migration processes. Results showed that the GO@peptide nanoassemblies not only effectively induced toxicity in the prostate cancer cells, but also strongly blocked the cell migration and inhibited the prostaglandin-mediated inflammatory process both in PC-3 and in HRECs. Moreover, the cytotoxic mechanism and the internalization efficiency of the theranostic nanoplatforms, investigated by mitochondrial ROS production analyses and confocal microscopy imaging, unraveled a dose-dependent manifold mechanism of action performed by the hybrid nanoassemblies against the PC-3 cells, with the detection of the GO-characteristic cell wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for cancer therapy. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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26 pages, 6216 KiB  
Article
Hyaluronan-Metal Gold Nanoparticle Hybrids for Targeted Tumor Cell Therapy
by Vanessa Sanfilippo, Viviana Carmela Linda Caruso, Lorena Maria Cucci, Rosanna Inturri, Susanna Vaccaro and Cristina Satriano
Int. J. Mol. Sci. 2020, 21(9), 3085; https://doi.org/10.3390/ijms21093085 - 27 Apr 2020
Cited by 19 | Viewed by 3937
Abstract
In this study, a novel multifunctional nanoplatform based on core-shell nanoparticles of spherical gold nanoparticles (AuNPs) capped with low and high molecular weight (200 and 700 kDa) hyaluronic acid (HA), was assembled via a green, one-pot redox synthesis method at room temperature. A [...] Read more.
In this study, a novel multifunctional nanoplatform based on core-shell nanoparticles of spherical gold nanoparticles (AuNPs) capped with low and high molecular weight (200 and 700 kDa) hyaluronic acid (HA), was assembled via a green, one-pot redox synthesis method at room temperature. A multitechnique characterization approach by UV-visible spectroscopy, dynamic light scattering and atomic force microscopy pointed to the effective ‘surface decoration’ of the gold nanoparticles by HA, resulting in different grafting densities of the biopolymer chains at the surface of the metal nanoparticle, which in turn affected the physicochemical properties of the nanoparticles. Specifically, the spectral features of the gold plasmonic peak (and the related calculated optical size), the hydrodynamic diameter and the nanoparticle stability were found to depend on the molecular weight of the HA. The CD44-targeting capability of HA-functionalized gold nanoparticles was tested in terms of antibacterial activity and cytotoxicity. An enhanced inhibitory activity against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus was found, with a HA molecular weight (MW)-dependent trend for the HA-capped AuNPs compared to the bare, glucose-capped AuNPs. Cell viability assays performed on two CD44-positive cell models, namely normal human umbilical vein endothelial (HUVEC) and prostate tumor (PC-3) cells, in comparison with neuroblastoma cells (SH-SY5Y), which do not express the CD44 receptor, demonstrated an increased cytotoxicity in neuroblastoma compared to prostate cancer cells upon the cellular treatments by HA–AuNP compared to the bare AuNP, but a receptor-dependent perturbation effect on cytoskeleton actin and lysosomal organelles, as detected by confocal microscopy. These results highlighted the promising potentialities of the HA-decorated gold nanoparticles for selective cytotoxicity in cancer therapy. Confocal microscopy imaging of the two human tumor cell models demonstrated a membrane-confined uptake of HA-capped AuNP in the cancer cells that express CD44 receptors and the different perturbation effects related to molecular weight of HA wrapping the metallic core of the plasmonic nanoparticles on cellular organelles and membrane mobility. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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14 pages, 12230 KiB  
Article
The Intravitreal Injection of Lanosterol Nanoparticles Rescues Lens Structure Collapse at an Early Stage in Shumiya Cataract Rats
by Noriaki Nagai, Yuya Fukuoka, Kanta Sato, Hiroko Otake, Atsushi Taga, Mikako Oka, Noriko Hiramatsu and Naoki Yamamoto
Int. J. Mol. Sci. 2020, 21(3), 1048; https://doi.org/10.3390/ijms21031048 - 05 Feb 2020
Cited by 11 | Viewed by 3661
Abstract
We designed an intravitreal injection formulation containing lanosterol nanoparticles (LAN-NPs) via the bead mill method and evaluated the therapeutic effect of LAN-NPs on lens structure collapse and opacification using two rat cataract models (SCR-N, rats with slight lens structure collapse; SCR-C, rats with [...] Read more.
We designed an intravitreal injection formulation containing lanosterol nanoparticles (LAN-NPs) via the bead mill method and evaluated the therapeutic effect of LAN-NPs on lens structure collapse and opacification using two rat cataract models (SCR-N, rats with slight lens structure collapse; SCR-C, rats with the combination of a remarkable lens structure collapse and opacification). The particle size of lanosterol in the LAN-NPs was around 50–400 nm. A single injection of LAN-NPs (0.5%) supplied lanosterol into the lens for 48 h, and no irritation or muddiness was observed following repeated injections of LAN-NPs for 6 weeks (once every 2 days). Moreover, LAN-NPs repaired the slight collapse of the lens structure in SCR-N. Although the remarkable changes in the lens structure of SCR-C were not repaired by LAN-NP, the onset of opacification was delayed. In addition, the increase of cataract-related factors (Ca2+ contents, nitric oxide levels, lipid peroxidation and calpain activity levels) in the lenses of SCR-C was attenuated by the repeated injection of LAN-NPs. It is possible that a deficiency of lanosterol promotes the production of oxidative stress. In conclusion, it is difficult to improve serious structural collapse with posterior movement of the lens nucleus with a supplement of lanosterol via LAN-NPs. However, the intravitreal injection of LAN-NPs was found to repair the space and structural collapse in the early stages in the lenses. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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31 pages, 6443 KiB  
Article
Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study
by Gabriel N. A. Rego, Mariana P. Nucci, Javier B. Mamani, Fernando A. Oliveira, Luciana C. Marti, Igor S. Filgueiras, João M. Ferreira, Caroline C. Real, Daniele de Paula Faria, Paloma L. Espinha, Daianne M. C. Fantacini, Lucas E. B. Souza, Dimas T. Covas, Carlos A. Buchpiguel and Lionel F. Gamarra
Int. J. Mol. Sci. 2020, 21(3), 958; https://doi.org/10.3390/ijms21030958 - 31 Jan 2020
Cited by 35 | Viewed by 4002
Abstract
Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation [...] Read more.
Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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17 pages, 3234 KiB  
Article
Identification of Nanobodies against the Acute Myeloid Leukemia Marker CD33
by Ema Romão, Ahmet Krasniqi, Laila Maes, Camille Vandenbrande, Yann G.-J. Sterckx, Benoit Stijlemans, Cécile Vincke, Nick Devoogdt and Serge Muyldermans
Int. J. Mol. Sci. 2020, 21(1), 310; https://doi.org/10.3390/ijms21010310 - 02 Jan 2020
Cited by 17 | Viewed by 5043
Abstract
Nanobodies (Nbs) are the smallest antigen-binding, single domain fragments derived from heavy-chain-only antibodies from Camelidae. Among the several advantages over conventional monoclonal antibodies, their small size (12–15 kDa) allows them to extravasate rapidly, to show improved tissue penetration, and to clear rapidly from [...] Read more.
Nanobodies (Nbs) are the smallest antigen-binding, single domain fragments derived from heavy-chain-only antibodies from Camelidae. Among the several advantages over conventional monoclonal antibodies, their small size (12–15 kDa) allows them to extravasate rapidly, to show improved tissue penetration, and to clear rapidly from blood, which are important characteristics for cancer imaging and targeted radiotherapy. Herein, we identified Nbs against CD33, a marker for acute myeloid leukemia (AML). A total of 12 Nbs were generated against recombinant CD33 protein, out of which six bound natively CD33 protein, expressed on the surface of acute myeloid leukemia THP-1 cells. The equilibrium dissociation constants (KD) of these six Nbs and CD33 range from 4 to 270 nM, and their melting temperature (Tm) varies between 52.67 and 67.80 °C. None of these Nbs showed leukemogenicity activity in vitro. The selected six candidates were radiolabeled with 99mTc, and their biodistribution was evaluated in THP-1-tumor-bearing mice. The imaging results demonstrated the fast tumor-targeting capacity of the Nbs in vivo. Among the anti-CD33 Nbs, Nb_7 showed the highest tumor uptake (2.53 ± 0.69 % injected activity per gram (IA/g), with low background signal, except in the kidneys and bladder. Overall, Nb_7 exhibits the best characteristics to be used as an anti-CD33 targeting vehicle for future diagnostic or therapeutic applications. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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11 pages, 1422 KiB  
Article
The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells
by Chi-Ming Chan, Chien-Yu Hsiao, Hsin-Ju Li, Jia-You Fang, Der-Chen Chang and Chi-Feng Hung
Int. J. Mol. Sci. 2020, 21(1), 109; https://doi.org/10.3390/ijms21010109 - 23 Dec 2019
Cited by 22 | Viewed by 3272
Abstract
Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a crucial stimulator for choroidal neovascularization (CNV) in age-related macular degeneration and pathologic myopia, as well as retinal neovascularization in proliferative diabetic retinopathy. Retinal and choroidal endothelial cells play key roles [...] Read more.
Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a crucial stimulator for choroidal neovascularization (CNV) in age-related macular degeneration and pathologic myopia, as well as retinal neovascularization in proliferative diabetic retinopathy. Retinal and choroidal endothelial cells play key roles in the development of retinal and CNV, and subsequent fibrosis. At present, the effects of gold nanoparticles (AuNPs) on the VEGF-induced choroid-retina endothelial (RF/6A) cells are still unknown. In our study, we investigated the effects of AuNPs on RF/6A cell viabilities and cell adhesion to fibronectin, a major ECM protein of fibrovascular membrane. Furthermore, the inhibitory effects of AuNPs on RF/6A cell migration induced by VEGF and its signaling were studied. Methods: The cell viability assay was used to determine the viability of cells treated with AuNPs. The migration of RF/6A cells was assessed by the Transwell migration assay. The cell adhesion to fibronectin was examined by an adhesion assay. The VEGF-induced signaling pathways were determined by western blotting. Results: The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay revealed no cytotoxicity of AuNPs on RF/6A cells. AuNPs inhibited VEGF-induced RF/6A cell migration in a concentration-dependent manner but showed no significant effects on RF/6A cell adhesion to fibronectin. Inhibitory effects of AuNPs on VEGF-induced Akt/eNOS were found. Conclusions: These results suggest that AuNPs are an effective inhibitor of VEGF-induced RF/6A cell migration through the Akt/eNOS pathways, but they have no effects on their cell viabilities and cell adhesion to fibronectin. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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16 pages, 2960 KiB  
Article
Identification of New DR5 Agonistic Nanobodies and Generation of Multivalent Nanobody Constructs for Cancer Treatment
by Golnaz Sadeghnezhad, Ema Romão, Robert Bernedo-Navarro, Sam Massa, Khosro Khajeh, Serge Muyldermans and Sadegh Hassania
Int. J. Mol. Sci. 2019, 20(19), 4818; https://doi.org/10.3390/ijms20194818 - 27 Sep 2019
Cited by 17 | Viewed by 3396
Abstract
Current cancer therapeutics suffer from a lack of specificity in targeting tumor cells and cause severe side effects. Therefore, the design of highly specialized drugs comprising antibody derivatives inducing apoptosis in targeted cancer cells is considered to be a promising strategy. Drugs acting [...] Read more.
Current cancer therapeutics suffer from a lack of specificity in targeting tumor cells and cause severe side effects. Therefore, the design of highly specialized drugs comprising antibody derivatives inducing apoptosis in targeted cancer cells is considered to be a promising strategy. Drugs acting on death receptor 5 (DR5) such as DR5 agonist antibodies replacing “TNF-related apoptosis-inducing ligand” (TRAIL) offer feasible opportunities in this direction. Although such agonists provided good antitumor activity in preclinical studies, they were less effective in clinical studies, possibly due to a disturbed Fc interaction with Fc-γ receptors. Thus, multimerized antigen binding fragments without Fc have been proposed to increase their efficacy. We generated nanobodies (Nbs), recombinant variable domains of heavy chain-only antibodies of camelids, against the DR5 ectodomain. Nb24 and Nb28 had an affinity in the nM and sub-nM range, but only Nb28 competes with TRAIL for binding to DR5. Bivalent, trivalent, and tetravalent constructs were generated, as well as an innovative pentameric Nb complex, to provoke avidity effects. In our cellular assays, these trimeric, tetrameric, and pentameric Nbs have a higher apoptotic capacity than monomeric Nbs and seem to mimic the activity of the natural TRAIL ligand on various cancer cells. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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14 pages, 2439 KiB  
Article
Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved Properties as an Anticancer Agent
by Seyed Ebrahim Alavi, Sitah Muflih Al Harthi, Hasan Ebrahimi Shahmabadi and Azim Akbarzadeh
Int. J. Mol. Sci. 2019, 20(7), 1531; https://doi.org/10.3390/ijms20071531 - 27 Mar 2019
Cited by 36 | Viewed by 3178
Abstract
This study aims to improve the cytotoxicity and potency of cisplatin-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) for the treatment of lung cancer through the modulation of temperature and polyethylene glycol (PEG) concentration as effective factors affecting the NPs’ properties. The NPs were synthesized using [...] Read more.
This study aims to improve the cytotoxicity and potency of cisplatin-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) for the treatment of lung cancer through the modulation of temperature and polyethylene glycol (PEG) concentration as effective factors affecting the NPs’ properties. The NPs were synthesized using an anionic polymerization method and were characterized in terms of size, drug loading efficiency, drug release profile, cytotoxicity effects, drug efficacy, and drug side effects. In this regard, dynamic light scattering (DLS), scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) methods, and hematoxylin and eosin (H&E) staining were used. The results showed that the size and the drug loading efficiency of the synthesized spherical NPs were 355–386 nm and 14–19%, respectively. Also, the drug release profile showed a controlled and slow drug release pattern with approximately 10% drug release over 48 h. In addition, the NPs significantly increased the cytotoxicity of the cisplatin in vitro environment by approximately 2 times and enhanced the therapeutic effects of the drug in vivo environment by increasing the survival time of lung-cancer-bearing mice by 20% compared to the standard drug receiver group. Also, the nanoformulation decreased the drug toxicity in an in vivo environment. According to the results, increasing the temperature and PEG concentration improved the properties of the drug loading efficiency, drug release profile, and cytotoxicity effect of drug-loaded NPs. Consequently, the synthesized formulation increased the survival of tumor-bearing mice and simultaneously decreased the cisplatin toxicity effects. In conclusion, the prepared nanoformulation can be considered a promising candidate for further evaluation for possible therapeutic use in the treatment of lung cancer. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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Review

Jump to: Research

29 pages, 3226 KiB  
Review
Nanomaterials for Antiangiogenic Therapies for Cancer: A Promising Tool for Personalized Medicine
by Hashem O. Alsaab, Alanoud S. Al-Hibs, Rami Alzhrani, Khawlah K. Alrabighi, Aljawharah Alqathama, Akram Alwithenani, Atiah H. Almalki and Yusuf S. Althobaiti
Int. J. Mol. Sci. 2021, 22(4), 1631; https://doi.org/10.3390/ijms22041631 - 05 Feb 2021
Cited by 21 | Viewed by 4010
Abstract
Angiogenesis is one of the hallmarks of cancer. Several studies have shown that vascular endothelium growth factor (VEGF) plays a leading role in angiogenesis progression. Antiangiogenic medication has gained substantial recognition and is commonly administered in many forms of human cancer, leading to [...] Read more.
Angiogenesis is one of the hallmarks of cancer. Several studies have shown that vascular endothelium growth factor (VEGF) plays a leading role in angiogenesis progression. Antiangiogenic medication has gained substantial recognition and is commonly administered in many forms of human cancer, leading to a rising interest in cancer therapy. However, this treatment method can lead to a deteriorating outcome of resistance, invasion, distant metastasis, and overall survival relative to its cytotoxicity. Furthermore, there are significant obstacles in tracking the efficacy of antiangiogenic treatments by incorporating positive biomarkers into clinical settings. These shortcomings underline the essential need to identify additional angiogenic inhibitors that target numerous angiogenic factors or to develop a new method for drug delivery of current inhibitors. The great benefits of nanoparticles are their potential, based on their specific properties, to be effective mechanisms that concentrate on the biological system and control various important functions. Among various therapeutic approaches, nanotechnology has emerged as a new strategy for treating different cancer types. This article attempts to demonstrate the huge potential for targeted nanoparticles and their molecular imaging applications. Notably, several nanoparticles have been developed and engineered to demonstrate antiangiogenic features. This nanomedicine could effectively treat a number of cancers using antiangiogenic therapies as an alternative approach. We also discuss the latest antiangiogenic and nanotherapeutic strategies and highlight tumor vessels and their microenvironments. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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32 pages, 1549 KiB  
Review
Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations
by Gabriel Nery de Albuquerque Rego, Arielly da Hora Alves, Mariana Penteado Nucci, Javier Bustamante Mamani, Fernando Anselmo de Oliveira and Lionel Fernel Gamarra
Int. J. Mol. Sci. 2020, 21(12), 4490; https://doi.org/10.3390/ijms21124490 - 24 Jun 2020
Cited by 4 | Viewed by 3018
Abstract
Glioblastoma (GBM) is the most aggressive tumor type whose resistance to conventional treatment is mediated, in part, by the angiogenic process. New treatments involving the application of nanoformulations composed of encapsulated drugs coupled to peptide motifs that direct drugs to specific targets triggered [...] Read more.
Glioblastoma (GBM) is the most aggressive tumor type whose resistance to conventional treatment is mediated, in part, by the angiogenic process. New treatments involving the application of nanoformulations composed of encapsulated drugs coupled to peptide motifs that direct drugs to specific targets triggered in angiogenesis have been developed to reach and modulate different phases of this process. We performed a systematic review with the search criterion (Glioblastoma OR Glioma) AND (Therapy OR Therapeutic) AND (Nanoparticle) AND (Antiangiogenic OR Angiogenesis OR Anti-angiogenic) in Pubmed, Scopus, and Cochrane databases, in which 312 articles were identified; of these, only 27 articles were included after selection and analysis of eligibility according to the inclusion and exclusion criteria. The data of the articles were analyzed in five contexts: the characteristics of the tumor cells; the animal models used to induce GBM for antiangiogenic treatment; the composition of nanoformulations and their physical and chemical characteristics; the therapeutic anti-angiogenic process; and methods for assessing the effects on antiangiogenic markers caused by therapies. The articles included in the review were heterogeneous and varied in practically all aspects related to nanoformulations and models. However, there was slight variance in the antiangiogenic effect analysis. CD31 was extensively used as a marker, which does not provide a view of the effects on the most diverse aspects involved in angiogenesis. Therefore, the present review highlighted the need for standardization between the different approaches of antiangiogenic therapy for the GBM model that allows a more effective meta-analysis and that helps in future translational studies. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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17 pages, 1165 KiB  
Review
The Basic Properties of Gold Nanoparticles and their Applications in Tumor Diagnosis and Treatment
by Xue Bai, Yueying Wang, Zhiyun Song, Yanmin Feng, Yuanyuan Chen, Deyuan Zhang and Lin Feng
Int. J. Mol. Sci. 2020, 21(7), 2480; https://doi.org/10.3390/ijms21072480 - 03 Apr 2020
Cited by 190 | Viewed by 21802
Abstract
Gold nanoparticles (AuNPs) have been widely studied and applied in the field of tumor diagnosis and treatment because of their special fundamental properties. In order to make AuNPs more suitable for tumor diagnosis and treatment, their natural properties and the interrelationships between these [...] Read more.
Gold nanoparticles (AuNPs) have been widely studied and applied in the field of tumor diagnosis and treatment because of their special fundamental properties. In order to make AuNPs more suitable for tumor diagnosis and treatment, their natural properties and the interrelationships between these properties should be systematically and profoundly understood. The natural properties of AuNPs were discussed from two aspects: physical and chemical. Among the physical properties of AuNPs, localized surface plasmon resonance (LSPR), radioactivity and high X-ray absorption coefficient are widely used in the diagnosis and treatment of tumors. As an advantage over many other nanoparticles in chemicals, AuNPs can form stable chemical bonds with S-and N-containing groups. This allows AuNPs to attach to a wide variety of organic ligands or polymers with a specific function. These surface modifications endow AuNPs with outstanding biocompatibility, targeting and drug delivery capabilities. In this review, we systematically summarized the physicochemical properties of AuNPs and their intrinsic relationships. Then the latest research advancements and the developments of basic research and clinical trials using these properties are summarized. Further, the difficulties to be overcome and possible solutions in the process from basic laboratory research to clinical application are discussed. Finally, the possibility of applying the results to clinical trials was estimated. We hope to provide a reference for peer researchers to better utilize the excellent physicochemical properties of gold nanoparticles in oncotherapy. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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31 pages, 16740 KiB  
Review
Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer
by Anubhab Mukherjee, Vijay Sagar Madamsetty, Manash K. Paul and Sudip Mukherjee
Int. J. Mol. Sci. 2020, 21(2), 455; https://doi.org/10.3390/ijms21020455 - 10 Jan 2020
Cited by 63 | Viewed by 6628
Abstract
Angiogenesis is a process of generation of de-novo blood vessels from already existing vasculature. It has a crucial role in different physiological process including wound healing, embryonic development, and tumor growth. The methods by which therapeutic drugs inhibit tumor angiogenesis are termed as [...] Read more.
Angiogenesis is a process of generation of de-novo blood vessels from already existing vasculature. It has a crucial role in different physiological process including wound healing, embryonic development, and tumor growth. The methods by which therapeutic drugs inhibit tumor angiogenesis are termed as anti-angiogenesis cancer therapy. Developments of angiogenic inhibiting drugs have various limitations causing a barrier for successful treatment of cancer, where angiogenesis plays an important role. In this context, investigators developed novel strategies using nanotechnological approaches that have demonstrated inherent antiangiogenic properties or used for the delivery of antiangiogenic agents in a targeted manner. In this present article, we decisively highlight the recent developments of various nanoparticles (NPs) including liposomes, lipid NPs, protein NPs, polymer NPs, inorganic NPs, viral and bio-inspired NPs for potential application in antiangiogenic cancer therapy. Additionally, the clinical perspectives, challenges of nanomedicine, and future perspectives are briefly analyzed. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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20 pages, 3995 KiB  
Review
Lab-On-A-Chip for the Development of Pro-/Anti-Angiogenic Nanomedicines to Treat Brain Diseases
by Subhathirai Subramaniyan Parimalam, Simona Badilescu, Nahum Sonenberg, Rama Bhat and Muthukumaran Packirisamy
Int. J. Mol. Sci. 2019, 20(24), 6126; https://doi.org/10.3390/ijms20246126 - 05 Dec 2019
Cited by 5 | Viewed by 3534
Abstract
There is a huge demand for pro-/anti-angiogenic nanomedicines to treat conditions such as ischemic strokes, brain tumors, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Nanomedicines are therapeutic particles in the size range of 10–1000 nm, where the drug is encapsulated into nano-capsules [...] Read more.
There is a huge demand for pro-/anti-angiogenic nanomedicines to treat conditions such as ischemic strokes, brain tumors, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Nanomedicines are therapeutic particles in the size range of 10–1000 nm, where the drug is encapsulated into nano-capsules or adsorbed onto nano-scaffolds. They have good blood–brain barrier permeability, stability and shelf life, and able to rapidly target different sites in the brain. However, the relationship between the nanomedicines’ physical and chemical properties and its ability to travel across the brain remains incompletely understood. The main challenge is the lack of a reliable drug testing model for brain angiogenesis. Recently, microfluidic platforms (known as “lab-on-a-chip” or LOCs) have been developed to mimic the brain micro-vasculature related events, such as vasculogenesis, angiogenesis, inflammation, etc. The LOCs are able to closely replicate the dynamic conditions of the human brain and could be reliable platforms for drug screening applications. There are still many technical difficulties in establishing uniform and reproducible conditions, mainly due to the extreme complexity of the human brain. In this paper, we review the prospective of LOCs in the development of nanomedicines for brain angiogenesis–related conditions. Full article
(This article belongs to the Special Issue Nanomaterials for Pro-/Anti-Angiogenic Therapies)
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