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Nanoparticles Based on Smart Polymers for Biomedical Applications
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Nanoparticles Based on Smart Polymers for Biomedical Applications

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

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 29919

Special Issue Editors

Prof. Dr. Marcel Popa

E-Mail Website
Guest Editor
“Cristofor Simionescu” Faculty of Chemical Engineering and Environment Protection, “Gheorghe Asachi” Technical University, Iasi, Romania
Interests: polysaccharide modification; bioactive polymers; biomaterials; hydrogels; interpenetrated networks; micro- and nanoparticles (spheres and capsules); hybrid and functionalized nanoparticles for drug targeting; drug delivery; polymer–drug conjugates
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Leonard-Ionut Atanase

E-Mail Website
Guest Editor
1. Department of Biomaterials, Faculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, Romania
2. Academy of Romanian Scientists, 050045 Bucharest, Romania
Interests: block and graft copolymers; micelles; colloids; emulsions; drug delivery; polysaccharides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will focus on fundamental research with practical applications of drug delivery systems based on smart polymers in the field of nanomedicine. Within the wide variety of these systems, we are interested in the preparation and characterization of pH, thermo-, and/or light-sensitive natural and synthetic polymers. Different types of drug-loaded nanoparticles, such as micelles, nanocapsules, nanogels, polymersomes, and nanospheres, are of practical interest. Another domain of interest is that of nanoparticles, functionalized with specific ligands or loaded with magnetic nanoparticles, for active targeted drug delivery.

Prof. Dr. Leonard Atanase
Prof. Dr. Marcel Popa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • smart polymers
  • micelles
  • nanogels
  • drug delivery
  • magnetic nanoparticles
  • active targeting

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Published Papers (6 papers)

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Research

Jump to: Review

24 pages, 3763 KiB  
Article
Polysaccharides-Based Complex Particles’ Protective Role on the Stability and Bioactivity of Immobilized Curcumin
by Camelia-Elena Iurciuc (Tincu), Leonard Ionuţ Atanase, Christine Jérôme, Vincent Sol, Patrick Martin, Marcel Popa and Lăcrămioara Ochiuz
Int. J. Mol. Sci. 2021, 22(6), 3075; https://doi.org/10.3390/ijms22063075 - 17 Mar 2021
Cited by 30 | Viewed by 3319
Abstract
The curcumin degradation represents a significant limitation for its applications. The stability of free curcumin (FC) and immobilized curcumin in complex particles (ComPs) based on different polysaccharides was studied under the action of several factors. Ultraviolet-visible (UV-VIS) and Fourier-transform infrared (FTIR) spectroscopy proved [...] Read more.
The curcumin degradation represents a significant limitation for its applications. The stability of free curcumin (FC) and immobilized curcumin in complex particles (ComPs) based on different polysaccharides was studied under the action of several factors. Ultraviolet-visible (UV-VIS) and Fourier-transform infrared (FTIR) spectroscopy proved the FC photodegradation and its role as a metal chelator: 82% of FC and between 26% and 39.79% of curcumin within the ComPs degraded after exposure for 28 days to natural light. The degradation half-life (t1/2) decreases for FC when the pH increases, from 6.8 h at pH = 3 to 2.1 h at pH = 9. For curcumin extracted from ComPs, t1/2 was constant (between 10 and 13 h) and depended on the sample’s composition. The total phenol (TPC) and total flavonoids (TFC) content values increased by 16% and 13%, respectively, for FC exposed to ultraviolet light at λ = 365 nm (UVA), whereas no significant change was observed for immobilized curcumin. Antioxidant activity expressed by IC50 (µmoles/mL) for FC exposed to UVA decreased by 29%, but curcumin within ComPs was not affected by the UVA. The bovine serum albumin (BSA) adsorption efficiency on the ComPs surface depends on the pH value and the cross-linking degree. ComPs have a protective role for the immobilized curcumin. Full article
(This article belongs to the Special Issue Nanoparticles Based on Smart Polymers for Biomedical Applications)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Curcumin degradation (%) of the free curcumin (FC) and the curcumin encapsulated in the P2C and P4C samples. All samples were exposed for 28 days to natural light and air.</p> Full article ">Figure 2
<p>Fourier-transform infrared (FTIR) spectrum for degraded curcumin in the presence of light and air for 28 days compared to the FTIR spectrum of non-degraded curcumin.</p> Full article ">Figure 3
<p>The theoretical structure of the curcumin/metal ions complex.</p> Full article ">Figure 4
<p>FTIR spectrum for free curcumin (FC) compared with the FTIR spectrum for the curcumin complexes with copper (CCu) and zinc (CZn) ions.</p> Full article ">Figure 5
<p>Ultraviolet (UV) spectra for FC, FC complexes with Cu<sup>2+</sup> and Zn<sup>2+</sup> ions (<b>a</b>) and for curcumin extracted from the P2C sample, which was previously immersed for 4 h in copper and zinc sulfate solutions (<b>b</b>).</p> Full article ">Figure 6
<p>Variation of non-degraded degraded curcumin in time at different pH values for free curcumin (FC) and curcumin immobilized P2C and P4C samples.</p> Full article ">Figure 7
<p>Variation in time in the amount of undegraded curcumin at pH 6.8 for free curcumin and curcumin extracted from P2C ComPs or P4C ComPs.</p> Full article ">Figure 8
<p>R<sub>S/FC</sub> variation in function of pH values of the buffer solutions.</p> Full article ">Figure 9
<p>The total content of phenols (orange) and flavonoids (green) in free curcumin (FC) and the curcumin extracted from the P2C, P4C, and P5C samples that were irradiated and non-irradiated with UVA. Results were expressed as mean value ± standard deviation (SD). The samples exposed to UVA light were noted with P2CUV, P4CUV, or P5CUV and FCUV.</p> Full article ">Figure 10
<p>IC<sub>50</sub> values on DPPH radical scavenging assay for free curcumin (FC) and curcumin extracted from P2C, P4C, and P5C samples before and after exposure to UV light for 30 min at 365 nm.</p> Full article ">Figure 11
<p>Bovine serum albumin (BSA) adsorption efficiency (AE%) for all samples obtained after simultaneous placement of the ComPs at pH = 2 (blue), pH = 6.8 (red), and pH = 7.4 (green). Results are expressed as mean values ± SD.</p> Full article ">
17 pages, 5392 KiB  
Article
Folate-Targeted Transgenic Activity of Dendrimer Functionalized Selenium Nanoparticles In Vitro
by Nikita Simone Pillay, Aliscia Daniels and Moganavelli Singh
Int. J. Mol. Sci. 2020, 21(19), 7177; https://doi.org/10.3390/ijms21197177 - 29 Sep 2020
Cited by 22 | Viewed by 3064
Abstract
Current chemotherapeutic drugs, although effective, lack cell-specific targeting, instigate adverse side effects in healthy tissue, exhibit unfavourable bio-circulation and can generate drug-resistant cancers. The synergistic use of nanotechnology and gene therapy, using nanoparticles (NPs) for therapeutic gene delivery to cancer cells is hereby [...] Read more.
Current chemotherapeutic drugs, although effective, lack cell-specific targeting, instigate adverse side effects in healthy tissue, exhibit unfavourable bio-circulation and can generate drug-resistant cancers. The synergistic use of nanotechnology and gene therapy, using nanoparticles (NPs) for therapeutic gene delivery to cancer cells is hereby proposed. This includes the benefit of cell-specific targeting and exploitation of receptors overexpressed in specific cancer types. The aim of this study was to formulate dendrimer-functionalized selenium nanoparticles (PAMAM-SeNPs) containing the targeting moiety, folic acid (FA), for delivery of pCMV-Luc-DNA (pDNA) in vitro. These NPs and their gene-loaded nanocomplexes were physicochemically and morphologically characterized. Nucleic acid-binding, compaction and pDNA protection were assessed, followed by cell-based in vitro cytotoxicity, transgene expression and apoptotic assays. Nanocomplexes possessed favourable sizes (<150 nm) and ζ-potentials (>25 mV), crucial for cellular interaction, and protected the pDNA from degradation in an in vivo simulation. PAMAM-SeNP nanocomplexes exhibited higher cell viability (>85%) compared to selenium-free nanocomplexes (approximately 75%), confirming the important role of selenium in these nanocomplexes. FA-conjugated PAMAM-SeNPs displayed higher overall transgene expression (HeLa cells) compared to their non-targeting counterparts, suggesting enhanced receptor-mediated cellular uptake. Overall, our results bode well for the use of these nano-delivery vehicles in future in vivo studies. Full article
(This article belongs to the Special Issue Nanoparticles Based on Smart Polymers for Biomedical Applications)
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Figure 1

Figure 1
<p>Scheme for the synthesis of poly(amidoamine) dendrimers (PAMAM)-selenium (Se)-folic acid (FA).</p> Full article ">Figure 2
<p>UV-visible absorption spectra of Selenium nanoparticles (SeNPs), PAMAM (G5), PAMAM-SeNPs, PAMAM-FA and PAMAM-Se-FA.</p> Full article ">Figure 3
<p>TEM images of (<b>A</b>) SeNPs, (<b>B</b>) PAMAM-FA, (<b>C</b>) PAMAM-Se-FA (<b>D</b>) PAMAM-FA-pDNA, (<b>E</b>) PAMAM-Se-FA-pDNA and (<b>F</b>) PAMAM-Se-pDNA.</p> Full article ">Figure 4
<p>Band shift assay lane 1 (control): 0.25 µg/µL pDNA and lanes 2–8: 0.25 µg/µL pDNA complexed to varying amounts of NP (µg/µL) as follows: (<b>A</b>) PAMAM (0.02, 0.04, 0.06, 0.08, 0.10 and 0.12), (<b>B</b>) PAMAM-Se (0.25, 0.5, 0.75, 1.0, 1.25 and 1.5), (<b>C</b>) PAMAM-FA (0.25, 0.5, 0.75, 1.0, 1.25 and 1.5) and (<b>D</b>) PAMAM-Se-FA (0.25, 0.5, 0.75, 0.1, 1.25 and 1.5). Arrows indicate optimal binding of pDNA to NP.</p> Full article ">Figure 5
<p>Serum nuclease protection assay depicting pDNA integrity after exposure to serum nucleases: lane 1 (positive control): 0.25 µg pDNA and lanes 2 (negative control): nuclease digested pDNA (0.25 µg). (<b>A</b>) Lanes 3–5: PAMAM nanocomplexes and lanes 6–8: PAMAM-Se nanocomplexes. (<b>B</b>) Lanes 3–5: PAMAM-FA nanocomplexes and lanes 6–8: PAMAM-Se-FA nanocomplexes.</p> Full article ">Figure 6
<p>Ethidium bromide displacement depicting the DNA-binding affinity of PAMAM, PAMAM-Se, PAMAM–FA and PAMAM-Se-FA: results are depicted as means ± SD (<span class="html-italic">n</span> = 3).</p> Full article ">Figure 7
<p>Cell viability (%) of HEK293, MCF-7, HeLa and SKBR-3 cells after treatment with (<b>A</b>) PAMAM, (<b>B</b>) PAMAM-SeNP, (<b>C</b>) PAMAM-FA and (<b>D</b>) PAMAM-Se-FA nanocomplexes at the suboptimal, optimal and supraoptimal ratios: the results are depicted as means ± SD (<span class="html-italic">n</span> = 3). (* <span class="html-italic">p</span> &lt; 0.005 and <span class="html-italic">** p</span> &lt; 0.01 vs. control).</p> Full article ">Figure 8
<p>Fluorescent images of dual-stained (acridine orange/ethidium bromide (AO/EB)) cells transfected with PAMAM, PAMAM-SeNP, PAMAM-FA and PAMAM-Se-FA nanocomplexes in HEK293, MCF-7, HeLa and SKBR-3 cells: the stained cells were viewed under an Olympus inverted fluorescence microscope (200× magnification) with a CC12 fluorescence camera (Olympus Co., Tokyo, Japan). Scale bar = 100 µm. L—live cells, EA—early apoptosis and LA—late apoptosis.</p> Full article ">Figure 9
<p>Apoptotic indices calculated for each nanocomplex at the observed optimal ratios in the selected cell lines: the results are depicted as means ± SD (<span class="html-italic">n</span> = 3). <span class="html-italic">(* p</span> &lt; 0.005 and <span class="html-italic">** p</span> &lt; 0.01 vs. PAMAM).</p> Full article ">Figure 10
<p>Luciferase activity in HEK293, MCF-7, HeLa and SKBR-3 cells transfected with (<b>A</b>) PAMAM, (<b>B</b>) PAMAM-Se (<b>C</b>) PAMAM-FA and (<b>D</b>) PAMAM-Se-FA nanocomplexes at the suboptimal, optimal and supraoptimal ratios: the results are depicted as means ± SD (<span class="html-italic">n</span> = 3). (* <span class="html-italic">p</span> &lt; 0.005 and ** <span class="html-italic">p</span> &lt; 0.01 vs. control).</p> Full article ">
19 pages, 4367 KiB  
Article
Antitumoral Drug: Loaded Hybrid Nanocapsules Based on Chitosan with Potential Effects in Breast Cancer Therapy
by Kheira Zanoune Dellali, Delia Mihaela Rata, Marcel Popa, M’hamed Djennad, Abdallah Ouagued and Daniela Gherghel
Int. J. Mol. Sci. 2020, 21(16), 5659; https://doi.org/10.3390/ijms21165659 - 7 Aug 2020
Cited by 10 | Viewed by 3263
Abstract
Cancer remains one of the world’s most devastating diseases and is responsible for more than 20% of all deaths. It is defined as uncontrolled proliferation of cells and spreads rapidly to healthy tissue. Controlled drug delivery systems offers great opportunities for the development [...] Read more.
Cancer remains one of the world’s most devastating diseases and is responsible for more than 20% of all deaths. It is defined as uncontrolled proliferation of cells and spreads rapidly to healthy tissue. Controlled drug delivery systems offers great opportunities for the development of new non-invasive strategies for the treatment of cancers. The main advantage of these systems is their capacity to accumulate in tumors via enhanced permeability and retention effects. In the present study, an innovative hybrid drug delivery system based on nanocapsules obtained from the interfacial condensation between chitosan and poly(N-vinyl pyrrolidone-alt-itaconic anhydride) and containing both magnetic nanoparticles and an antitumoral drug was developed in order to improve the efficiency of the antitumoral treatment. Using dynamic light scattering, it was observed that the mean diameter of these hybrid nanocapsules was in the range of 43 to 142 nm. SEM confirmed their nanometric size and their well-defined spherical shape. These nanocapsules allowed the encapsulation of an increased amount of 5-fluorouracil and provided controlled drug release. In vitro studies have revealed that these drug-loaded hybrid nanocapsules were able to induce a cytostatic effect on breast carcinoma MCF-7 cell lines (Human Caucasian breast adenocarcinoma - HTB-22) comparable to that of the free drug. Full article
(This article belongs to the Special Issue Nanoparticles Based on Smart Polymers for Biomedical Applications)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Schematic illustration of magnetic NCs based on CS and poly(NVPAI) containing magnetic nanoparticles.</p> Full article ">Figure 2
<p>FTIR spectra for magnetite (M), CN, CNM-1, and CNM-4.</p> Full article ">Figure 3
<p>Dimensional distribution curves of magnetic nanoparticles (M) and hybrid nanocapsules (CNM).</p> Full article ">Figure 4
<p>Scanning electron microscopy (SEM) for sample CNM-5.</p> Full article ">Figure 5
<p>Transmission electron microscopy (TEM) for sample CNM-5 (<b>a</b>,<b>b</b>) with two different magnifications.</p> Full article ">Figure 6
<p>Thermogravimetric curves for CN, CNM-1, CNM-4, and CNM-6.</p> Full article ">Figure 7
<p>The magnetization curves of different magnetic NCs.</p> Full article ">Figure 8
<p>The swelling kinetics curves of the NCs in alkaline conditions (pH 7.4) for the following samples: (<b>a</b>) CN, CNM-1, CNM-2, CNM-3, CNM-4, CNM-5; (<b>b</b>) CN, CNM-4, CNM-6, CNM-7, CNM-8.</p> Full article ">Figure 9
<p>In vitro release kinetics of 5-FU from magnetic NCs in phosphate buffer solution (pH 7.4), with a zoom insert of release kinetics between 0 and 30 min for samples: (<b>a</b>) CNM-1, CNM-4 and CNM-5; (<b>b</b>) CNM-4, CNM-6, CNM-7 and CNM-8.</p> Full article ">Figure 10
<p>Experimental release kinetics and theoretical Korsmeyer–Peppas curves for magnetic nanocapsules.</p> Full article ">Figure 11
<p>Viability of human breast carcinoma MCF-7 cells after 48 h incubation with non-loaded nanocapsules (CN-2), 5-FU-loaded nanocapsules (CN-2-5-FU), 5-FU-loaded magnetic nanocapsules (CNM-4-5-FU), and 5-FU as a function of concentration (Student’s <span class="html-italic">t</span> test: * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001).</p> Full article ">

Review

Jump to: Research

23 pages, 40917 KiB  
Review
The Benefits of Smart Nanoparticles in Dental Applications
by Silvia Vasiliu, Stefania Racovita, Ionela Aurica Gugoasa, Maria-Andreea Lungan, Marcel Popa and Jacques Desbrieres
Int. J. Mol. Sci. 2021, 22(5), 2585; https://doi.org/10.3390/ijms22052585 - 4 Mar 2021
Cited by 43 | Viewed by 6710
Abstract
Dentistry, as a branch of medicine, has undergone continuous evolution over time. The scientific world has focused its attention on the development of new methods and materials with improved properties that meet the needs of patients. For this purpose, the replacement of so-called [...] Read more.
Dentistry, as a branch of medicine, has undergone continuous evolution over time. The scientific world has focused its attention on the development of new methods and materials with improved properties that meet the needs of patients. For this purpose, the replacement of so-called “passive” dental materials that do not interact with the oral environment with “smart/intelligent” materials that have the capability to change their shape, color, or size in response to an externally stimulus, such as the temperature, pH, light, moisture, stress, electric or magnetic fields, and chemical compounds, has received much attention in recent years. A strong trend in dental applications is to apply nanotechnology and smart nanomaterials such as nanoclays, nanofibers, nanocomposites, nanobubbles, nanocapsules, solid-lipid nanoparticles, nanospheres, metallic nanoparticles, nanotubes, and nanocrystals. Among the nanomaterials, the smart nanoparticles present several advantages compared to other materials, creating the possibility to use them in various dental applications, including preventive dentistry, endodontics, restoration, and periodontal diseases. This review is focused on the recent developments and dental applications (drug delivery systems and restoration materials) of smart nanoparticles. Full article
(This article belongs to the Special Issue Nanoparticles Based on Smart Polymers for Biomedical Applications)
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Figure 1

Figure 1
<p>Properties of dental materials.</p> Full article ">Figure 2
<p>Types of smart materials.</p> Full article ">Figure 3
<p>Graphical representation of composite resins.</p> Full article ">Figure 4
<p>Advantages and disadvantages of composite materials used in dental restoration.</p> Full article ">Figure 5
<p>Setting reaction of glass ionomer cements.</p> Full article ">Figure 6
<p>Properties of resin-modified glass ionomers compared with glass ionomers.</p> Full article ">Figure 7
<p>Dental nanomaterials available on the market.</p> Full article ">
20 pages, 1934 KiB  
Review
Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake
by Parinaz Sabourian, Ghazaleh Yazdani, Seyed Sajad Ashraf, Masoud Frounchi, Shohreh Mashayekhan, Sahar Kiani and Ashok Kakkar
Int. J. Mol. Sci. 2020, 21(21), 8019; https://doi.org/10.3390/ijms21218019 - 28 Oct 2020
Cited by 128 | Viewed by 7894
Abstract
Cellular internalization of inorganic, lipidic and polymeric nanoparticles is of great significance in the quest to develop effective formulations for the treatment of high morbidity rate diseases. Understanding nanoparticle–cell interactions plays a key role in therapeutic interventions, and it continues to be a [...] Read more.
Cellular internalization of inorganic, lipidic and polymeric nanoparticles is of great significance in the quest to develop effective formulations for the treatment of high morbidity rate diseases. Understanding nanoparticle–cell interactions plays a key role in therapeutic interventions, and it continues to be a topic of great interest to both chemists and biologists. The mechanistic evaluation of cellular uptake is quite complex and is continuously being aided by the design of nanocarriers with desired physico-chemical properties. The progress in biomedicine, including enhancing the rate of uptake by the cells, is being made through the development of structure–property relationships in nanoparticles. We summarize here investigations related to transport pathways through active and passive mechanisms, and the role played by physico-chemical properties of nanoparticles, including size, geometry or shape, core-corona structure, surface chemistry, ligand binding and mechanical effects, in influencing intracellular delivery. It is becoming clear that designing nanoparticles with specific surface composition, and engineered physical and mechanical characteristics, can facilitate their internalization more efficiently into the targeted cells, as well as enhance the rate of cellular uptake. Full article
(This article belongs to the Special Issue Nanoparticles Based on Smart Polymers for Biomedical Applications)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Uptake of gold nanoparticles (GNPs). Hyperspectral image of cell uptake of (<b>a</b>) 20-nm- and (<b>c</b>) 50-nm-sized GNPs; (<b>b</b>,<b>d</b>) GNPs clusters mapped using reflectance spectra of GNPs; (<b>e</b>) GNP internalization per cell for 20- and 50-nm-sized GNPs in two different cell lines. (<b>f</b>,<b>g</b>) The reflectance spectra of the 20- and 50-nm-sized GNPs in the monolayers (<b>a</b>,<b>c</b>). Reprinted with permission from [<a href="#B55-ijms-21-08019" class="html-bibr">55</a>]. Copyright 2016 Springer Nature.</p> Full article ">Figure 2
<p>Quantification of the internalization of mesoporous silica NPs: fluorescence intensity (<b>A</b>), particle numbers (<b>B</b>), using fluorescent-activated cell sorting (FACS). ** Indicates statistical significance, <span class="html-italic">p</span> &lt; 0.01). Reprinted with permission from [<a href="#B70-ijms-21-08019" class="html-bibr">70</a>]. Copyright 2010 Elsevier.</p> Full article ">Figure 3
<p>(<b>A</b>) Kinetics of cell uptake of fluorescently labeled silica NPs (25 μg/mL) in the complete (cMEM) and serum-free (SF) media, measured by flowcytometry; (<b>B</b>) curve in cMEM from A alone. Reprinted with permission from [<a href="#B77-ijms-21-08019" class="html-bibr">77</a>]. Copyright 2012 American Chemical Society.</p> Full article ">Figure 4
<p>Nanocapsular stiffness effects: (<b>a</b>) cellular uptake by RAW264.7 murine macrophages of surface-modified NPs; (<b>b</b>) fluorescence micrographs showing the cellular uptake of FA-PEG-modified NPs by CytD-treated SKOV3 cells. (** Indicates statistical significance, <span class="html-italic">p</span> &lt; 0.01). Reprinted with permission from [<a href="#B114-ijms-21-08019" class="html-bibr">114</a>]. Copyright 2018 American Chemical Society.</p> Full article ">Scheme 1
<p>Active and passive cell uptake of particles: (<b>A</b>) phagocytosis, (<b>B</b>) caveolin-mediated endocytosis, (<b>C</b>) clathrin–caveolin-independent endocytosis, (<b>D</b>) clathrin-mediated endocytosis, (<b>E</b>) macro-pinocytosis, (<b>F</b>) ion pumps, (<b>G</b>) exocytosis, (<b>H</b>) facilitated diffusion, and (<b>I</b>) simple diffusion.</p> Full article ">Scheme 2
<p>Different mechanisms of nanoparticle (NP) phagocytosis: (<b>A</b>) CR3-mediated phagocytosis occurs by sinking NPs through CR3-receptors; (<b>B</b>) zipper mode phagocytosis via Fcγ-receptors including cell progression; (<b>C</b>) trigger mode phagocytosis with no receptors takes place through stimulating ruffles around particles.</p> Full article ">Scheme 3
<p>Protein corona formation on the surface of NPs: (<b>A</b>) adsorption of smaller proteins to NP surface by rapid diffusion, (<b>B</b>) replacement of small proteins by larger ones, reconfiguration of proteins and final hard and soft corona formation (<b>C</b>).</p> Full article ">
29 pages, 745 KiB  
Review
Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma
by Stefano Burgio, Leila Noori, Antonella Marino Gammazza, Claudia Campanella, Mariantonia Logozzi, Stefano Fais, Fabio Bucchieri, Francesco Cappello and Celeste Caruso Bavisotto
Int. J. Mol. Sci. 2020, 21(15), 5432; https://doi.org/10.3390/ijms21155432 - 30 Jul 2020
Cited by 37 | Viewed by 4432
Abstract
Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use [...] Read more.
Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well. Full article
(This article belongs to the Special Issue Nanoparticles Based on Smart Polymers for Biomedical Applications)
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Figure 1

Figure 1
<p>Strategy of EVs modification for therapeutic purposes. The figure schematizes the approaches currently used in EVs engineering or in the manipulation of their content. (<b>1</b>) The EVs are promising candidates in the treatment of numerous pathologies and there are various reliable sources. EVs can be isolated from the cell culture supernatant of various producing cell lines, from body fluids and also from food. (<b>2</b>) The EVs molecular composition is complex and it depends on the cellular source. They can contain different classes of proteins (membrane-bound tetraspanins CD9, CD81 and CD63; receptors, heat shock proteins), ncRNAs (RNAs; MicroRNAs) and lipids (lysobisphosphatidic acid; phosphatidylcholine; phosphatidylethanolamine and sphingomyelin). (<b>3</b>) The different methods to manipulate the EVs content include the preloading approach, in which a pre-existing endogenous cargo is the therapeutic molecule. In the display technology, the EV-producing cells can be engineered with a plasmid in order to induce the expression of exogenous proteins. The post-loading method consists in the direct introduction of drug molecules into EVs after their isolation. (<b>4</b>) The engineered EVs may also be manipulated to be more bioactive and bioavailable and can be administered to patients for the MPM therapy.</p> Full article ">
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