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Nanomaterials
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Surface Modification and Functionalization of Nanoparticles
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Surface Modification and Functionalization of Nanoparticles

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (20 October 2021) | Viewed by 28685

Special Issue Editor

Prof. Dr. Jose L. Arias

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Guest Editor
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja s/n, 18071 Granada, Spain
Interests: active drug targeting; biomedical applications of colloids and nanoparticles; biopharmacy; drug absorption; drug delivery; drug release; formulation and evaluation of pharmaceutical dosage forms; hyperthermia-based anticancer treatment; in vivo fate of nanoplatforms; ligand-receptor interactions and nanoparticle endocytosis; long-circulating nanoparticles; magnetic colloids; nanoteranosis; passive drug targeting; PEGylated nanoparticles; pharmaceutical technology; pharmacokinetics; stimuli sensitive nanostructures; surface chemistry and interface science; surface functionalization of nanoparticles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tailoring surface chemistry has contributed to the perfect control of the biological fate of nanomedicines, while assuring their colloidal stability in vitro and in vivo. To that aim, the nanoparticle surface is chemically modified using appropriate polymeric stabilizers/surfactants, by generating polymeric shells, and/or by the formation of lipid-like coatings. As a consequence, a specific in vivo targeting is possible thanks to the enhanced permeability and retention (EPR) effect. Additionally, the delivery of therapeutic molecules (and imaging agents) to the targeted tissue/cell can be maximized if this passive targeting strategy is combined with the surface decoration of the nanomedicine (or theranostic particle) with biomolecules determining specific recognition mechanisms, i.e., ligand-mediated drug targeting.

Surface functionalization of nanoplatforms has also been advantageously used in cell labeling and imaging, tissue engineering, cell separation and cell sensing, separation of biochemicals, enzyme/protein immobilization, bioanalysis, and immunoassays, just to mention some additional applications in Biomedicine. Interestingly, surface decorated nanoparticles have also found uses far from Biomedicine, e.g., catalysis, energy-based research, and environmental applications.

This Special Issue of Nanomaterials aims at receiving contributions (in the form of research articles, letters, reviews, and communications) to update the basis, applications, and perspectives in the surface engineering of nanoparticles, including the most promising moves towards advanced chemical surface modifications. I kindly invite you to submit a contribution to this Special Issue of Nanomaterials “Surface Modification and Functionalization of Nanoparticles”.

Prof. Dr. Jose L. Arias
Guest Editor

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. Nanomaterials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • Biomedical applications
  • Enhanced permeation and retention effect
  • Environmental applications
  • Ligand-mediated delivery of drugs, genes, and imaging agents
  • Nanoparticle
  • Passive drug targeting
  • Theranosis

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Published Papers (6 papers)

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Research

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14 pages, 17392 KiB  
Article
Label-Free, Rapid and Facile Gold-Nanoparticles-Based Assay as a Potential Spectroscopic Tool for Trastuzumab Quantification
by Ahmed Alsadig, Hendrik Vondracek, Paolo Pengo, Lucia Pasquato, Paola Posocco, Pietro Parisse and Loredana Casalis
Nanomaterials 2021, 11(12), 3181; https://doi.org/10.3390/nano11123181 - 24 Nov 2021
Cited by 3 | Viewed by 3095
Abstract
Monoclonal antibody-based immunotherapy is one of the pillars of cancer treatment. However, for an efficient and personalized approach to the therapy, a quantitative evaluation of the right dose for each patient is required. In this study, we developed a simple, label-free, and rapid [...] Read more.
Monoclonal antibody-based immunotherapy is one of the pillars of cancer treatment. However, for an efficient and personalized approach to the therapy, a quantitative evaluation of the right dose for each patient is required. In this study, we developed a simple, label-free, and rapid approach to quantify Trastuzumab, a humanized IgG1 monoclonal antibody used against human epidermal growth factor receptor 2 (HER2), overexpressed in breast cancer patients, based on localized surface plasmon resonance (LSPR). The central idea of this work was to use gold nanoparticles (AuNPs) as plasmonic scaffolds, decorated with HER2 binders mixed with oligo-ethylene glycol (OEG) molecules, to tune the surface density of the attached macromolecules and to minimize nonspecific binding events. Specifically, we characterized and optimized a self-assembled monolayer of mixed alkylthiols terminated with nitrilotriacetic acid (NTA), and OEG3 as a spacing ligand to achieve both excellent dispersibility and high reliability in protein immobilization. The successful immobilization of histidine-tagged HER2 (His-tagged HER2) on NTA via cobalt (II) chelates was demonstrated, confirming the fully functional attachment of the proteins to the AuNP surface. The proposed design demonstrates the capability of producing a clear readout that enables the transduction of a Trastuzumab/HER2 binding event into optical signals based on the wavelength shifts in LSPR, which allowed for detecting clinically relevant concentrations of Trastuzumab down to 300 ng/mL in the buffer and 2 µg/mL in the diluted serum. This strategy was found to be fast and highly specific to Trastuzumab. These findings make the present platform an auspicious tool for developing affordable bio-nanosensors. Full article
(This article belongs to the Special Issue Surface Modification and Functionalization of Nanoparticles)
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17 pages, 3195 KiB  
Article
Retention of Activity by Antibodies Immobilized on Gold Nanoparticles of Different Sizes: Fluorometric Method of Determination and Comparative Evaluation
by Dmitriy V. Sotnikov, Nadezhda A. Byzova, Anatoly V. Zherdev and Boris B. Dzantiev
Nanomaterials 2021, 11(11), 3117; https://doi.org/10.3390/nano11113117 - 18 Nov 2021
Cited by 14 | Viewed by 2567
Abstract
Antibody–nanoparticle conjugates are widely used analytical reagents. An informative parameter reflecting the conjugates’ properties is the number of antibodies per nanoparticle that retain their antigen-binding ability. Estimation of this parameter is characterized by a lack of simple, reproducible methods. The proposed method is [...] Read more.
Antibody–nanoparticle conjugates are widely used analytical reagents. An informative parameter reflecting the conjugates’ properties is the number of antibodies per nanoparticle that retain their antigen-binding ability. Estimation of this parameter is characterized by a lack of simple, reproducible methods. The proposed method is based on the registration of fluorescence of tryptophan residues contained in proteins and combines sequential measurements of first the immobilized antibody number and then the bound protein antigen number. Requirements for the measurement procedure have been determined to ensure reliable and accurate results. Using the developed technique, preparations of spherical gold nanoparticles obtained by the most common method of citrate reduction of gold salts (the Turkevich–Frens method) and varying in average diameter from 15 to 55 nm have been characterized. It was shown that the number of antibodies (immunoglobulins G) bound by one nanoparticle ranged from 30 to 194 during adsorptive unoriented monolayer immobilization. C-reactive protein was considered as the model antigen. The percentage of antibody valences that retained their antigen-binding properties in the conjugate increased from 17 to 34% with an increase in the diameter of gold nanoparticles. The proposed method and the results of the study provide tools to assess the capabilities of the preparations of gold nanoparticles and their conjugates as well as the expediency of seeking the best techniques for various practical purposes. Full article
(This article belongs to the Special Issue Surface Modification and Functionalization of Nanoparticles)
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16 pages, 1418 KiB  
Article
Silver Nanoparticles Stable to Oxidation and Silver Ion Release Show Size-Dependent Toxicity In Vivo
by Brittany Cunningham, Arek M. Engstrom, Bryan J. Harper, Stacey L. Harper and Marilyn R. Mackiewicz
Nanomaterials 2021, 11(6), 1516; https://doi.org/10.3390/nano11061516 - 8 Jun 2021
Cited by 48 | Viewed by 5580
Abstract
Silver nanoparticles (AgNPs) are widely used in commerce, however, the effect of their physicochemical properties on toxicity remains debatable because of the confounding presence of Ag+ ions. Thus, we designed a series of AgNPs that are stable to surface oxidation and Ag [...] Read more.
Silver nanoparticles (AgNPs) are widely used in commerce, however, the effect of their physicochemical properties on toxicity remains debatable because of the confounding presence of Ag+ ions. Thus, we designed a series of AgNPs that are stable to surface oxidation and Ag+ ion release. AgNPs were coated with a hybrid lipid membrane comprised of L-phosphatidylcholine (PC), sodium oleate (SOA), and a stoichiometric amount of hexanethiol (HT) to produce oxidant-resistant AgNPs, Ag–SOA–PC–HT. The stability of 7-month aged, 20–100 nm Ag–SOA–PC–HT NPs were assessed using UV–Vis, dynamic light scattering (DLS), and inductively coupled plasma mass spectrometry (ICP-MS), while the toxicity of the nanomaterials was assessed using a well-established, 5-day embryonic zebrafish assay at concentrations ranging from 0–12 mg/L. There was no change in the size of the AgNPs from freshly made samples or 7-month aged samples and minimal Ag+ ion release (<0.2%) in fishwater (FW) up to seven days. Toxicity studies revealed AgNP size- and concentration-dependent effects. Increased mortality and sublethal morphological abnormalities were observed at higher concentrations with smaller nanoparticle sizes. This study, for the first time, determined the effect of AgNP size on toxicity in the absence of Ag+ ions as a confounding variable. Full article
(This article belongs to the Special Issue Surface Modification and Functionalization of Nanoparticles)
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16 pages, 2846 KiB  
Article
Engineering Modular Half-Antibody Conjugated Nanoparticles for Targeting CD44v6-Expressing Cancer Cells
by Bianca N. Lourenço, Rúben F. Pereira, Cristina C. Barrias, Claudia Fischbach, Carla Oliveira and Pedro L. Granja
Nanomaterials 2021, 11(2), 295; https://doi.org/10.3390/nano11020295 - 23 Jan 2021
Cited by 12 | Viewed by 4362
Abstract
Gastric cancer (GC) remains a major cause of death worldwide mainly because of the late detection in advanced stage. Recently, we proposed CD44v6 as a relevant marker for early detection of GC, opening new avenues for GC-targeted theranostics. Here, we designed a modular [...] Read more.
Gastric cancer (GC) remains a major cause of death worldwide mainly because of the late detection in advanced stage. Recently, we proposed CD44v6 as a relevant marker for early detection of GC, opening new avenues for GC-targeted theranostics. Here, we designed a modular nanoscale system that selectively targets CD44v6-expressing GC cells by the site-oriented conjugation of a new-engineered CD44v6 half-antibody fragment to maleimide-modified polystyrene nanoparticles (PNPs) via an efficient bioorthogonal thiol-Michael addition click chemistry. PNPs with optimal particle size (200 nm) for crossing a developed biomimetic CD44v6-associated GC stromal model were further modified with a heterobifunctional maleimide crosslinker and click conjugated to the novel CD44v6 half-antibody fragment, obtained by chemical reduction of full antibody, without affecting its bioactivity. Collectively, our results confirmed the specific targeting ability of CD44v6-PNPs to CD44v6-expressing cells (1.65-fold higher than controls), highlighting the potential of CD44v6 half-antibody conjugated nanoparticles as promising and clinically relevant tools for the early diagnosis and therapy of GC. Additionally, the rational design of our nanoscale system may be explored for the development of several other nanotechnology-based disease-targeted approaches. Full article
(This article belongs to the Special Issue Surface Modification and Functionalization of Nanoparticles)
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13 pages, 1499 KiB  
Article
Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein
by Rossella De Marco, Enrico Rampazzo, Junwei Zhao, Luca Prodi, Mayra Paolillo, Pierre Picchetti, Francesca Gallo, Natalia Calonghi and Luca Gentilucci
Nanomaterials 2020, 10(6), 1211; https://doi.org/10.3390/nano10061211 - 21 Jun 2020
Cited by 6 | Viewed by 3363
Abstract
Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the [...] Read more.
Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the preparation and in vitro validation of a synthetic mimic of Smac/DIABLO, based on fluorescent polyethylene glycol (PEG)-coated silica-core nanoparticles (NPs) carrying a Smac/DIABLO-derived pro-apoptotic peptide and a tumor-homing integrin peptide ligand. At low μM concentration, the NPs showed significant toxicity towards A549, U373, and HeLa cancer cells and modest toxicity towards other integrin-expressing cells, correlated with integrin-mediated cell uptake and consequent highly increased levels of apoptotic activity, without perturbing cells not expressing the α5 integrin subunit. Full article
(This article belongs to the Special Issue Surface Modification and Functionalization of Nanoparticles)
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Review

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34 pages, 18115 KiB  
Review
Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines
by Mazen M. El-Hammadi and José L. Arias
Nanomaterials 2022, 12(3), 354; https://doi.org/10.3390/nano12030354 - 22 Jan 2022
Cited by 55 | Viewed by 7508
Abstract
Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to [...] Read more.
Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review. Full article
(This article belongs to the Special Issue Surface Modification and Functionalization of Nanoparticles)
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