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Pharmaceutics
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Cancer Nanomedicine—From the Bench to the Bedside
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Cancer Nanomedicine—From the Bench to the Bedside

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 25332

Special Issue Editor

Prof. Dr. Sabrina Pricl

E-Mail Website
Guest Editor
Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS), Department of Engineering and Architecture, University of Trieste, 34127 Trieste, Italy
Interests: nanomedicine; molecular oncology; molecular biology; structural biology; medicinal chemistry; molecular medicine; nanotechnology; nanoscience; drug and gene delivery; cancer-targeted therapy; drug delivery system design; computer-assisted drug design
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer remains the major cause of morbidity and mortality in the world, and its incidence has been steadily increasing since 1980. Cancer kills more people on a global scale than AIDS, malaria, and tuberculosis combined and accounts for 14 million new cases and 8 million related deaths in yearly. In the western world, cancer represents the second leading cause of death after cardiovascular diseases. Moreover, the impact of cancer in the developing world is growing at an alarming rate, and low- and middle-income countries are projected to account for two thirds of all cases of cancer worldwide by 2050. 

As we all know, finding efficient non-invasive imaging systems to be used in diagnosing cancer and/or novel effective anticancer therapies are two urgent and still unresolved problems and, in the fight against this disease, scientists are devoting tremendous efforts towards the utilization of nanomedicines. Nanotechnology-based reporter and therapeutic systems exhibit major benefits with respect to conventional tracers and active agents, including—among others—higher imaging resolution, improved half-life, more efficient tumor targeting, enhanced therapeutic action and drug resistance bypass, and reduced side effects. Unfortunately, only a few nanodiagnostics and nanotherapeutics have reached the commercial level, most still being in the investigational phase. 

Accordingly, this Special Issue aims at gathering state-of-the-art efforts in the development of new, reliable, efficient, and effective nanosystems for cancer imaging and anticancer nanotherapeutics (nanomedicine and/or nanosystems carrying anticancer agents (from small drugs to biologics and genetic materials) from their initial design to the relevant preclinical testing of efficacy, pharmacokinetics, and toxicity.

In particular, we welcome the submission of contributions focused on nanosystems for cancer imaging/anticancer nanotherapeutics and dealing with one or more of the following aspects:·      

  • Computer-assisted design, synthesis, and optimization of new covalent or self-assembled chemical entities as cancer nanomedicines and/or nanosystems carrying anticancer agents;·      
  • Physicochemical and structural characterization;·      
  • In vitro and in vivo studies, including (a) cellular uptake and localization of the compounds, (b) controlled release, (c) mechanism of the anticancer activity, (d) efficacy assessment in relevant oncology models (xenografts/syngeneic models), (e) ADME (absorption, distribution, metabolism and elimination) properties; (f) characterization and modeling of the pharmacokinetics/pharmacodynamics (PK/PD) relationship, (g) ability to elude the immune system long enough to release a therapeutic cargo, and (h) safety and toxicology studies in clinically relevant animal models.

Prof. Sabrina Pricl
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. Pharmaceutics is an international peer-reviewed open access monthly 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

  • cancer nanomedicines
  • cancer imaging nanosystems
  • cancer nanotherapeutics
  • synthesis
  • characterization
  • in vitro testing
  • in vivo testing

Related Special Issue

Published Papers (5 papers)

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Research

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14 pages, 2848 KiB  
Article
Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer
by Hajer Ziouziou, Clément Paris, Sébastien Benizri, Thi Khanh Le, Claudia Andrieu, Dang Tan Nguyen, Ananda Appavoo, David Taïeb, Frédéric Brunel, Ridha Oueslati, Olivier Siri, Michel Camplo, Philippe Barthélémy and Palma Rocchi
Pharmaceutics 2021, 13(5), 623; https://doi.org/10.3390/pharmaceutics13050623 - 27 Apr 2021
Cited by 4 | Viewed by 2171
Abstract
Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor 4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt [...] Read more.
Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor 4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt Hsp27/eIF4E interaction and significantly delay castration-resistant tumor progression in prostate cancer xenografts. In the present work, various strategies of encapsulation of phenazine #14 with either DOTAU (N-[5′-(2′,3′-dioleoyl)uridine]-N′,N′,N′-trimethylammonium tosylate) and DOU-PEG2000 (5′-PEG2000-2′,3′-dioleoyluridine) nucleolipids (NLs) were developed in order to improve its solubilization, biological activity, and bioavailability. We observed that NLs-encapsulated phenazine #14-driven Hsp27-eIF4E interaction disruption increased cytotoxic effects on castration-resistant prostate cancer cell line and inhibited tumor growth in castration-resistant prostate cancer cell xenografted mice compared to phenazine #14 and NLs alone. Phenazine #14 NL encapsulation might represent an interesting nanostrategy for CRPC therapy. Full article
(This article belongs to the Special Issue Cancer Nanomedicine—From the Bench to the Bedside)
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19 pages, 2927 KiB  
Article
Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery
by Beatriz Giesen, Ann-Christin Nickel, Juri Barthel, Ulf Dietrich Kahlert and Christoph Janiak
Pharmaceutics 2021, 13(2), 295; https://doi.org/10.3390/pharmaceutics13020295 - 23 Feb 2021
Cited by 7 | Viewed by 2813
Abstract
Gold nanoparticles (Au NPs) are studied as delivery systems to enhance the effect of the glutaminase1 inhibitor CB839, a promising drug candidate already in clinical trials for tumor treatments. Au NPs were synthesized using a bottom-up approach and covered with polymers able to [...] Read more.
Gold nanoparticles (Au NPs) are studied as delivery systems to enhance the effect of the glutaminase1 inhibitor CB839, a promising drug candidate already in clinical trials for tumor treatments. Au NPs were synthesized using a bottom-up approach and covered with polymers able to bind CB839 as a Au-polymer-CB839 conjugate. The drug loading efficiency (DLE) was determined using high-performance liquid chromatography and characterization of the CB839-loaded NPs was done with various microscopic and spectroscopic methods. Despite the chemical inertness of CB839, Au NPs were efficient carriers with a DLE of up to 12%, depending on the polymer used. The therapeutic effect of CB839 with and without Au was assessed in vitro in 2D and 3D glioblastoma (GBM) cell models using different assays based on the colony formation ability of GBM stem cells (GSCs). To avoid readout disturbances from the Au metal, viability methods which do not require optical detection were hereby optimized. These showed that Au NP delivery increased the efficacy of CB839 in GSCs, compared to CB839 alone. Fluorescent microscopy proved successful NP penetration into the GSCs. With this first attempt to combine CB839 with Au nanotechnology, we hope to overcome delivery hurdles of this pharmacotherapy and increase bioavailability in target sites. Full article
(This article belongs to the Special Issue Cancer Nanomedicine—From the Bench to the Bedside)
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17 pages, 2950 KiB  
Article
Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine
by Alba Martín-Moreno, José L. Jiménez Blanco, Jamie Mosher, Douglas R. Swanson, José M. García Fernández, Ajit Sharma, Valentín Ceña and María Angeles Muñoz-Fernández
Pharmaceutics 2020, 12(7), 656; https://doi.org/10.3390/pharmaceutics12070656 - 11 Jul 2020
Cited by 12 | Viewed by 3309
Abstract
Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response [...] Read more.
Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response. Full article
(This article belongs to the Special Issue Cancer Nanomedicine—From the Bench to the Bedside)
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14 pages, 3437 KiB  
Article
pH-Sensitive Folic Acid Conjugated Alginate Nanoparticle for Induction of Cancer-Specific Fluorescence Imaging
by Sara Lee and Kangwon Lee
Pharmaceutics 2020, 12(6), 537; https://doi.org/10.3390/pharmaceutics12060537 - 11 Jun 2020
Cited by 9 | Viewed by 3406
Abstract
In cancer nanomedicine, numerous studies have been conducted on the surface modification and transport capacity of nanoparticles (NPs); however, biological barriers, such as enzymatic degradation or non-specific delivery during circulation, remain to be cleared. Herein, we developed pH-sensitive NPs that degrade in an [...] Read more.
In cancer nanomedicine, numerous studies have been conducted on the surface modification and transport capacity of nanoparticles (NPs); however, biological barriers, such as enzymatic degradation or non-specific delivery during circulation, remain to be cleared. Herein, we developed pH-sensitive NPs that degrade in an acidic environment and release 5-aminolevulinic acid (5ALA) to the target site. NPs were prepared by conjugating alginate with folic acid, followed by encapsulation of 5ALA through a water-in-oil (W/O) emulsion method. The alginate-conjugated folic acid nanoparticles (AF NPs) were homogeneous in size, stable for a long time in aqueous suspension without aggregation, and non-toxic. AF NPs were small enough to efficiently infiltrate tumors (<50 nm) and were specifically internalized by cancer cells through receptor-mediated endocytosis. After the intracellular absorption of NPs, alginate was deprotonated in the lysosomes and released 5ALA, which was converted to protoporphyrin IX (PpIX) through mitochondrial heme synthesis. Our study outcomes demonstrated that AF NPs were not degraded by enzymes or other external factors before reaching cancer cells, and fluorescent precursors were specifically and accurately delivered to cancer cells to generate fluorescence. Full article
(This article belongs to the Special Issue Cancer Nanomedicine—From the Bench to the Bedside)
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Review

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22 pages, 1266 KiB  
Review
Endocytosis: The Nanoparticle and Submicron Nanocompounds Gateway into the Cell
by Darío Manzanares and Valentín Ceña
Pharmaceutics 2020, 12(4), 371; https://doi.org/10.3390/pharmaceutics12040371 - 17 Apr 2020
Cited by 246 | Viewed by 12610
Abstract
Nanoparticles (NPs) and submicron particles are increasingly used as carriers for delivering therapeutic compounds to cells. Their entry into the cell represents the initial step in this delivery process, being most of the nanoparticles taken up by endocytosis, although other mechanisms can contribute [...] Read more.
Nanoparticles (NPs) and submicron particles are increasingly used as carriers for delivering therapeutic compounds to cells. Their entry into the cell represents the initial step in this delivery process, being most of the nanoparticles taken up by endocytosis, although other mechanisms can contribute to the uptake. To increase the delivery efficiency of therapeutic compounds by NPs and submicron particles is very relevant to understand the mechanisms involved in the uptake process. This review covers the proposed pathways involved in the cellular uptake of different NPs and submicron particles types as well as the role that some of the physicochemical nanoparticle characteristics play in the uptake pathway preferentially used by the nanoparticles to gain access and deliver their cargo inside the cell. Full article
(This article belongs to the Special Issue Cancer Nanomedicine—From the Bench to the Bedside)
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