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Targeted Nanodelivery systems for Oncology Applications

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A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 35790

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Special Issue Editors

Dr. Zahra Rattray

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Guest Editor

Strathclyde Institute Of Pharmacy And Biomedical Sciences, University of Strathclyde, Glasgow G1 1XQ, UK
Interests: biologics; nanomedicines; cancer; drug delivery; bioanalysis

Dr. Friedrich Philipp Seib

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Guest Editor

Strathclyde Institute Of Pharmacy And Biomedical Sciences, University of Strathclyde, Glasgow G1 1XQ, UK
Interests: biopolymers; silk; stem cells; drug delivery;

Dr. Asha Kumari Patel

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Guest Editor

Faculty of Medicine, National Heart & Lung Institute, Imperial College London, London SW7 2BX, UK
Interests: gene therapy; nucleic acid therapeutics; biomaterials; regenerative medicine

Special Issue Information

Dear Colleagues,

Worldwide, 50% of people will be diagnosed with cancer during their lifetime, and with cancer remaining a leading cause of mortality worldwide, new chemotherapies are urgently needed.

The nanotherapeutic market is projected to reach a net worth of GBP 600 billion by 2025, with 50 products in the clinic and a wave of new-generation innovator products reaching the market. This rapid growth in global investment in nanoscale delivery systems is owing to the discovery of novel biomolecular targets and an enhanced understanding of tumor biology, advances in the engineering of new materials, and new chemistries for the selective targeting of tumor vulnerabilities that have increased the translational potential of a diverse and versatile range of targeting ligands, carrier systems and hybrid molecules at an unprecedented scale and speed.

Combined with the increased clinical implementation of precision medicine and a more advanced understanding of the biomolecular drivers of cancer, reporting on advances in the development of next-generation targeted and selective delivery vehicles has never been so timely. This Special Issue is aimed at providing the nanomedicine community with a holistic overview of advances in the design and synthesis of novel nanoscale materials for drug delivery, as well as evaluations of their physicochemical parameters and interactions with biological systems (in vitro/in vivo).

In this Special Issue, we welcome the submission of full articles, short communications, and review articles presenting novel concepts regarding targeted-nanomedicine-based drug delivery systems.

Dr. Zahra Rattray
Dr. Friedrich Philipp Seib
Dr. Asha Kumari Patel
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. Bioengineering 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 2700 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

nanomedicine
precision medicine
theranostics
gene therapy
drug delivery
nanoparticle
polymers
liposomes
monoclonal antibodies
exosomes
biomaterials
lipid nanoparticles
targeting ligands

Published Papers (7 papers)

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Research

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19 pages, 3661 KiB

Open AccessArticle

Ιnclusion Complexes of Magnesium Phthalocyanine with Cyclodextrins as Potential Photosensitizing Agents

by Eleni Kavetsou, Charalampos Tsoukalas-Koulas, Annita Katopodi, Alexandros Kalospyros, Eleni Alexandratou and Anastasia Detsi

Bioengineering 2023, 10(2), 244; https://doi.org/10.3390/bioengineering10020244 - 13 Feb 2023

Cited by 2 | Viewed by 1661

Abstract

In this work, the preparation of inclusion complexes, (ICs) using magnesium phthalocyanine (MgPc) and various cyclodextrins (β-CD, γ-CD, HP-β-CD, Me-β-CD), using the kneading method is presented. Dynamic light scattering (DLS) indicated that the particles in dispersion possessed mean size values between 564 to 748 nm. The structural characterization of the ICs by infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy provides evidence of the formation of the ICs. The release study of the MgPc from the different complexes was conducted at pH 7.4 and 37 °C, and indicated that a rapid release (“burst effect”) of ~70% of the phthalocyanine occurred in the first 20 min. The kinetic model that best describes the release profile is the Korsmeyer–Peppas. The photodynamic therapy studies against the squamous carcinoma A431 cell line indicated a potent photosensitizing activity of MgPc (33% cell viability after irradiation for 3 min with 18 mW/cm²), while the ICs also presented significant activity. Among the different ICs, the γ-CD-MgPc IC exhibited the highest photokilling capacity under the same conditions (cell viability 26%). Finally, intracellular localization studies indicated the enhanced cellular uptake of MgPc after incubation of the cells with the γ-CD-MgPc complex for 4 h compared to MgPc in its free form. Full article

(This article belongs to the Special Issue Targeted Nanodelivery systems for Oncology Applications)

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18 pages, 2929 KiB

Open AccessArticle

The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents

by Nagwa El-Baz, Betty M. Nunn, Paula J. Bates and Martin G. O’Toole

Bioengineering 2022, 9(12), 766; https://doi.org/10.3390/bioengineering9120766 - 04 Dec 2022

Cited by 4 | Viewed by 1654

Abstract

Gold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs with polyethylene glycol (PEG) is a widely used practice in research in order to decrease opsonization of the particles by serum proteins and to decrease particle uptake by the mononuclear phagocyte system. We investigated the impact of PEGylation on the formation of protein coronae and the subsequent uptake by macrophages and MDA-MB-231 cancer cells. Furthermore, we investigated the in vivo biodistribution in xenograft tumor-bearing mice using a library of 4 and 10 nm GNPs conjugated with a gadolinium chelate as MRI contrast agent, cancer-targeting aptamer AS1411 (or CRO control oligonucleotide), and with or without PEG molecules of different molecular weight (Mw: 1, 2, and 5 kDa). In vitro results showed that PEG failed to decrease the adsorption of proteins; moreover, the cellular uptake by macrophage cells was contingent on the different configurations of the aptamers and the length of the PEG chain. In vivo biodistribution studies showed that PEG increased the uptake by tumor cells for some GNPs, albeit it did not decrease the uptake of GNPs by macrophage-rich organs. Full article

(This article belongs to the Special Issue Targeted Nanodelivery systems for Oncology Applications)

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16 pages, 4456 KiB

Open AccessEditor’s ChoiceArticle

Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes

by Jaimin R. Shah, Tao Dong, Abraham T. Phung, Tony Reid, Christopher Larson, Ana B. Sanchez, Bryan Oronsky, Sarah L. Blair, Omonigho Aisagbonhi, William C. Trogler and Andrew C. Kummel

Bioengineering 2022, 9(11), 620; https://doi.org/10.3390/bioengineering9110620 - 27 Oct 2022

Cited by 2 | Viewed by 2221

Abstract

Adenovirus (Ad) is a widely studied viral vector for cancer therapy as it can be engineered to cause selective lysis of cancer cells. However, Ad delivery is limited in treating cancers that do not have coxsackievirus and adenovirus receptors (CAR). To overcome this challenge, Ad-encapsulated liposomes were developed that enhance the delivery of Ads and increase therapeutic efficacy. Cationic empty liposomes were manufactured first, to which an anionic Ad were added, which resulted in encapsulated Ad liposomes through charge interaction. Optimization of the liposome formula was carried out with series of formulation variables experiments using an extrusion process, which is ideal for laboratory-scale small batches. Later, the optimized formulation was manufactured with a homogenization technique—A high shear rotor-stator blending, that is ideal for large-scale manufacturing and is in compliance with Good Manufacturing Practices (GMP). Comparative in vitro transduction, physicochemical characterization, long-term storage stability at different temperature conditions, and in vivo animal studies were performed. Ad encapsulated liposomes transduced CAR deficient cells 100-fold more efficiently than the unencapsulated Ad (p ≤ 0.0001) in vitro, and 4-fold higher in tumors injected in nude mice in vivo. Both extrusion and homogenization performed similarly–with equivalent in vitro and in vivo transduction efficiencies, physicochemical characterization, and long-term storage stability. Thus, two Ad encapsulated liposomes preparation methods used herein, i.e., extrusion vs. homogenization were equivalent in terms of enhanced Ad performance and long-term storage stability; this will, hopefully, facilitate translation to the clinic. Full article

(This article belongs to the Special Issue Targeted Nanodelivery systems for Oncology Applications)

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23 pages, 3412 KiB

Open AccessArticle

Anti-EpCAM Functionalized I-131 Radiolabeled Biomimetic Nanocarrier Sodium/Iodide-Symporter-Mediated Breast-Cancer Treatment

by Suphalak Khamruang Marshall, Yada Panrak, Naritsara Makchuchit, Passara Jaroenpakdee, Boonyisa Saelim, Maneerat Taweesap and Verachai Pachana

Bioengineering 2022, 9(7), 294; https://doi.org/10.3390/bioengineering9070294 - 30 Jun 2022

Cited by 5 | Viewed by 21226

Abstract

Currently, breast-cancer treatment has a number of adverse side effects and is associated with poor rates of progression-free survival. Therefore, a radiolabeled anti-EpCAM targeted biomimetic coated nanocarrier (EINP) was developed in this study to overcome some of the treatment challenges. The double emulsion method synthesized the poly(lactic-co-glycolic acid) (PLGA) nanoparticle with Na¹³¹I entrapped in the core. The PLGA nanoparticle was coated in human red blood cell membranes and labeled with epithelial cell adhesion molecule (EpCAM) antibody to enable it to target EpCAM overexpression by breast-cancer cells. Characterization determined the EINP size as 295 nm, zeta potential as −35.9 mV, and polydispersity as 0.297. EINP radiochemical purity was >95%. Results determined the EINP efficacy against EpCAM positive MCF-7 breast cancer at 24, 48, and 72 h were 69.11%, 77.84%, and 74.6%, respectively, demonstrating that the EINPs achieved greater cytotoxic efficacy supported by NIS-mediated Na¹³¹I uptake than the non-targeted ¹³¹INPs and Na¹³¹I. In comparison, fibroblast (EpCAM negative) treated with EINPs had significantly lower cytotoxicity than Na¹³¹I and ¹³¹INPs (p < 0.05). Flow cytometry fluorescence imaging visually signified delivery by EINPs specifically to breast-cancer cells as a result of anti-EpCAM targeting. Additionally, the EINP had a favorable safety profile, as determined by hemolysis. Full article

(This article belongs to the Special Issue Targeted Nanodelivery systems for Oncology Applications)

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Review

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16 pages, 1723 KiB

Open AccessReview

Review on Biomedical Advances of Hybrid Nanocomposite Biopolymeric Materials

by Abeer M. Alosaimi, Randa O. Alorabi, Dina F. Katowah, Zahrah T. Al-Thagafi, Eman S. Alsolami, Mahmoud A. Hussein, Mohammad Qutob and Mohd Rafatullah

Bioengineering 2023, 10(3), 279; https://doi.org/10.3390/bioengineering10030279 - 21 Feb 2023

Cited by 2 | Viewed by 1789

Abstract

Hybrid materials are classified as one of the most highly important topics that have been of great interest to many researchers in recent decades. There are many species that can fall under this category, one of the most important of which contain biopolymeric materials as a matrix and are additionally reinforced by different types of carbon sources. Such materials are characterized by many diverse properties in a variety industrial and applied fields but especially in the field of biomedical applications. The biopolymeric materials that fall under this label are divided into natural biopolymers, which include chitosan, cellulose, and gelatin, and industrial or synthetic polymers, which include polycaprolactone, polyurethane, and conducting polymers of variable chemical structures. Furthermore, there are many types of carbon nanomaterials that are used as enhancers in the chemical synthesis of these materials as reinforcement agents, which include carbon nanotubes, graphene, and fullerene. This research investigates natural biopolymers, which can be composed of carbon materials, and the educational and medical applications that have been developed for them in recent years. These applications include tissue engineering, scaffold bones, and drug delivery systems. Full article

(This article belongs to the Special Issue Targeted Nanodelivery systems for Oncology Applications)

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22 pages, 3320 KiB

Open AccessReview

Broadening the Horizons of RNA Delivery Strategies in Cancer Therapy

by Shuaiying Wu, Chao Liu, Shuang Bai, Zhixiang Lu and Gang Liu

Bioengineering 2022, 9(10), 576; https://doi.org/10.3390/bioengineering9100576 - 19 Oct 2022

Cited by 4 | Viewed by 3330

Abstract

RNA-based therapy is a promising and innovative strategy for cancer treatment. However, poor stability, immunogenicity, low cellular uptake rate, and difficulty in endosomal escape are considered the major obstacles in the cancer therapy process, severely limiting the development of clinical translation and application. For efficient and safe transport of RNA into cancer cells, it usually needs to be packaged in appropriate carriers so that it can be taken up by the target cells and then be released to the specific location to perform its function. In this review, we will focus on up-to-date insights of the RNA-based delivery carrier and comprehensively describe its application in cancer therapy. We briefly discuss delivery obstacles in RNA-mediated cancer therapy and summarize the advantages and disadvantages of different carriers (cationic polymers, inorganic nanoparticles, lipids, etc.). In addition, we further summarize and discuss the current RNA therapeutic strategies approved for clinical use. A comprehensive overview of various carriers and emerging delivery strategies for RNA delivery, as well as the current status of clinical applications and practice of RNA medicines are classified and integrated to inspire fresh ideas and breakthroughs. Full article

(This article belongs to the Special Issue Targeted Nanodelivery systems for Oncology Applications)

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16 pages, 5079 KiB

Open AccessReview

Selected Flavonoids to Target Melanoma: A Perspective in Nanoengineering Delivery Systems

by Tiago E. Coutinho, Eliana B. Souto and Amélia M. Silva

Bioengineering 2022, 9(7), 290; https://doi.org/10.3390/bioengineering9070290 - 29 Jun 2022

Cited by 1 | Viewed by 1890

Abstract

Melanoma is a complex type of cancer that depends on several metabolic factors, while the currently used therapies are not always effective and have unwanted side effects. In this review, the main factors involved in the etiology of cutaneous carcinoma are highlighted, together with the main genes and proteins that regulate cancer invasion and metastization. The role of five selected flavonoids, namely, apigenin, epigallocatechin-3-gallate, kaempferol, naringenin, and silybin, in the modulating receptor tyrosine kinase (RTK) and Wnt pathways is reported with their relevance in the future design of drugs to mitigate and/or treat melanoma. However, as phenolic compounds have some difficulties in reaching the target site, the encapsulation of these compounds in nanoparticles is a promising strategy to promote improved physicochemical stabilization of the bioactives and achieve greater bioavailability. Scientific evidence is given about the beneficial effects of loading these flavonoids into selected nanoparticles for further exploitation in the treatment of melanoma. Full article

(This article belongs to the Special Issue Targeted Nanodelivery systems for Oncology Applications)

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