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Special Issue "Nanocarriers for Diagnostics, Imaging, and Drug Delivery: Critical Perspectives on Materials, Technologies, in Vivo Fate"

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

Deadline for manuscript submissions: 31 July 2020.

Special Issue Editors

Prof. Dr. Paola Luciani
Website SciProfiles
Guest Editor
Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland
Interests: liposomes and lipid-based nanocarriers; depot injectables; targeted delivery; contrast agents for fluorescence functional imaging; cell-derived therapeutics and diagnostics
Special Issues and Collections in MDPI journals
Prof. Dr. Davide Brambilla
Website
Guest Editor
University of Montreal, Montreal, Canada
Interests: drug delivery; biomaterials; micro- and nanotechnology; diagnostic devices

Special Issue Information

Dear Colleagues,

Miniaturizing drug delivery systems carries an arsenal of advantages along. In addition to improved biodistribution profiles and increased therapeutic indices, the large surface area available on nanocarriers discloses powerful possibilities to generate multifunctional platforms synergistically suited for therapeutic and diagnostic purposes. The early identification of diseases can be achieved thanks to an ever-growing knowledge on biomarkers, while the outcome of minimally invasive surgery can be dramatically improved by means of image-guided procedures fine-tuned by tailored nanocontrast agents. Nevertheless, despite the massive numbers of nanocarriers proposed, bottlenecks in providing clinically relevant results are constantly present. Are new materials proposed as building blocks keeping an eye on safety? Is the transition from an in vitro system to an in vivo one the rate-limiting step? Is a critical evaluation of the efficacy against relevant controls always rigorously conducted? Last but not least, the debate about the most successful approach is open today: Is a formulation-driven design or a disease-driven strategy ultimately more advisable?

With this Special Issue of Molecules, we aim at proposing an overview on some of the most recent approaches in the development of nanocarriers for imaging, diagnostic, and drug delivery, with a particular attention to studies involving in vivo evaluations.

We also warmly welcome contributions in the form of research articles, short communication, and review articles presenting prototype systems with a strong preclinical potential. New materials and biomaterials proposed as building block for the nanocarriers, hybrid nanocarriers, classical nanocarriers revisited for new imaging and diagnostic modalities, or alternative nano-based drug delivery approaches are among the themes that would fit this Special Issue’s vision. Submission of manuscripts critically presenting negative results as final outcome of robust working hypothesis is also strongly encouraged.

We look forward to receiving your contributions!

Prof. Dr. Paola Luciani
Prof. Dr. Davide Brambilla
Guest Editors

Keywords

  • nanocarriers
  • theranostics
  • diagnostic
  • imaging
  • drug delivery
  • multifunctional imaging
  • negative results
  • critical evaluations

Published Papers (5 papers)

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Research

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Open AccessArticle
Flame-Made Calcium Phosphate Nanoparticles with High Drug Loading for Delivery of Biologics
Molecules 2020, 25(7), 1747; https://doi.org/10.3390/molecules25071747 - 10 Apr 2020
Abstract
Nanoparticles exhibit potential as drug carriers in biomedicine due to their high surface-to-volume ratio that allows for facile drug loading. Nanosized drug delivery systems have been proposed for the delivery of biologics facilitating their transport across epithelial layers and maintaining their stability against [...] Read more.
Nanoparticles exhibit potential as drug carriers in biomedicine due to their high surface-to-volume ratio that allows for facile drug loading. Nanosized drug delivery systems have been proposed for the delivery of biologics facilitating their transport across epithelial layers and maintaining their stability against proteolytic degradation. Here, we capitalize on a nanomanufacturing process famous for its scalability and reproducibility, flame spray pyrolysis, and produce calcium phosphate (CaP) nanoparticles with tailored properties. The as-prepared nanoparticles are loaded with bovine serum albumin (model protein) and bradykinin (model peptide) by physisorption and the physicochemical parameters influencing their loading capacity are investigated. Furthermore, we implement the developed protocol by formulating CaP nanoparticles loaded with the LL-37 antimicrobial peptide, which is a biological drug currently involved in clinical trials. High loading values along with high reproducibility are achieved. Moreover, it is shown that CaP nanoparticles protect LL-37 from proteolysis in vitro. We also demonstrate that LL-37 retains its antimicrobial activity against Escherichia coli and Streptococcus pneumoniae when loaded on nanoparticles in vitro. Therefore, we highlight the potential of nanocarriers for optimization of the therapeutic profile of existing and emerging biological drugs. Full article
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Open AccessArticle
Trastuzumab Conjugated Superparamagnetic Iron Oxide Nanoparticles Labeled with 225Ac as a Perspective Tool for Combined α-Radioimmunotherapy and Magnetic Hyperthermia of HER2-Positive Breast Cancer
Molecules 2020, 25(5), 1025; https://doi.org/10.3390/molecules25051025 - 25 Feb 2020
Cited by 3
Abstract
It has been proven and confirmed in numerous repeated tests, that the use of a combination of several therapeutic methods gives much better treatment results than in the case of separate therapies. Particularly promising is the combination of ionizing radiation and magnetic hyperthermia [...] Read more.
It has been proven and confirmed in numerous repeated tests, that the use of a combination of several therapeutic methods gives much better treatment results than in the case of separate therapies. Particularly promising is the combination of ionizing radiation and magnetic hyperthermia in one drug. To achieve this objective, magnetite nanoparticles have been modified in their core with α emitter 225Ac, in an amount affecting only slightly their magnetic properties. By 3-phosphonopropionic acid (CEPA) linker nanoparticles were conjugated covalently with trastuzumab (Herceptin®), a monoclonal antibody that recognizes ovarian and breast cancer cells overexpressing the HER2 receptors. The synthesized bioconjugates were characterized by transmission electron microscopy (TEM), Dynamic Light Scattering (DLS) measurement, thermogravimetric analysis (TGA) and application of 131I-labeled trastuzumab for quantification of the bound biomolecule. The obtained results show that one 225[email protected]3O4-CEPA-trastuzumab bioconjugate contains an average of 8–11 molecules of trastuzumab. The labeled nanoparticles almost quantitatively retain 225Ac (>98%) in phosphate-buffered saline (PBS) and physiological salt, and more than 90% of 221Fr and 213Bi over 10 days. In human serum after 10 days, the fraction of 225Ac released from 225[email protected]3O4 was still less than 2%, but the retention of 221Fr and 213Bi decreased to 70%. The synthesized 225[email protected]3O4-CEPA-trastuzumab bioconjugates have shown a high cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptor in-vitro. The in-vivo studies indicate that this bioconjugate exhibits properties suitable for the treatment of cancer cells by intratumoral or post-resection injection. The intravenous injection of the 225[email protected]3O4-CEPA-trastuzumab radiobioconjugate is excluded due to its high accumulation in the liver, lungs and spleen. Additionally, the high value of a specific absorption rate (SAR) allows its use in a new very perspective combination of α radionuclide therapy with magnetic hyperthermia. Full article
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Open AccessArticle
Synthesis of Ultrastable Gold Nanoparticles as a New Drug Delivery System
Molecules 2019, 24(16), 2929; https://doi.org/10.3390/molecules24162929 - 13 Aug 2019
Cited by 2
Abstract
Nanotechnologies are increasingly being developed for medical purposes. However, these nanomaterials require ultrastability for better control of their pharmacokinetics. The present study describes three types of ultrastable gold nanoparticles stabilized by thiolated polyethylene glycol groups remaining intact when subjected to some of the [...] Read more.
Nanotechnologies are increasingly being developed for medical purposes. However, these nanomaterials require ultrastability for better control of their pharmacokinetics. The present study describes three types of ultrastable gold nanoparticles stabilized by thiolated polyethylene glycol groups remaining intact when subjected to some of the harshest conditions described thus far in the literature, such as autoclave sterilization, heat and freeze-drying cycles, salts exposure, and ultracentrifugation. Their stability is characterized by transmission electron microscopy, UV-visible spectroscopy, and dynamic light scattering. For comparison purposes, two conventional nanoparticle types were used to assess their colloidal stability under all conditions. The ability of ultrastable gold nanoparticles to encapsulate bimatoprost, a drug for glaucoma treatment, is demonstrated. MTS assays on human corneal epithelial cells is assessed without changing cell viability. The impact of ultrastable gold nanoparticles on wound healing dynamics is assessed on tissue engineered corneas. These results highlight the potential of ultrastable gold nanoparticles as a drug delivery system in ocular therapy. Full article
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Review

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Open AccessReview
Promising Approach in the Treatment of Glaucoma Using Nanotechnology and Nanomedicine-Based Systems
Molecules 2019, 24(20), 3805; https://doi.org/10.3390/molecules24203805 - 22 Oct 2019
Cited by 2
Abstract
Glaucoma is considered a leading cause of blindness with the human eye being one of the body’s most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye’s peculiar and exclusive anatomy and physiology continue [...] Read more.
Glaucoma is considered a leading cause of blindness with the human eye being one of the body’s most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye’s peculiar and exclusive anatomy and physiology continue to pose a significant obstacle to researchers and pharmacologists in the provision of efficient drug delivery. Though several traditional invasive and noninvasive eye therapies exist, including implants, eye drops, and injections, there are still significant complications that arise which may either be their low bioavailability or the grave ocular adverse effects experienced thereafter. On the other hand, new nanoscience technology and nanotechnology serve as a novel approach in ocular disease treatment. In order to interact specifically with ocular tissues and overcome ocular challenges, numerous active molecules have been modified to react with nanocarriers. In the general population of glaucoma patients, disease growth and advancement cannot be contained by decreasing intraocular pressure (IOP), hence a spiking in future research for novel drug delivery systems and target therapeutics. This review focuses on nanotechnology and its therapeutic and diagnostic prospects in ophthalmology, specifically glaucoma. Nanotechnology and nanomedicine history, the human eye anatomy, research frontiers in nanomedicine and nanotechnology, its imaging modal quality, diagnostic and surgical approach, and its possible application in glaucoma will all be further explored below. Particular focus will be on the efficiency and safety of this new therapy and its advances. Full article
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Other

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Open AccessBrief Report
Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy
Molecules 2020, 25(8), 1994; https://doi.org/10.3390/molecules25081994 - 24 Apr 2020
Cited by 1
Abstract
Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is [...] Read more.
Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo. Full article
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