Special Issue "Novel Nanoparticles for Targeted Delivery of Therapeutic Nucleic Acids"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 31 October 2021.

Special Issue Editors

Dr. Aristides D. Tagalakis
E-Mail Website
Guest Editor
Department of Biology, Edge Hill University, Ormskirk L39 4QP, UK
Interests: gene therapy; RNA delivery; nucleic acid therapeutics; gene editing; nonviral vectors; cancer; respiratory disorders; ocular disorders; cardiovascular disorders; rare diseases
Dr. Cynthia Yu-Wai-Man
E-Mail Website
Guest Editor
King's College London, London SE1 7EH, UK
Interests: glaucoma; fibrosis; conjunctival transcriptomics; targeted therapeutics; precision medicine; clinical trials

Special Issue Information

Dear Colleagues,

With the completion of the Human Genome project, there was great excitement about deciphering disease-causing genes. Since then, a number of them has been identified, but still, there are only few diseases which have seen some therapeutic outcomes. Over the years, many scientists have worked in genetic therapies, and only recently has some success been realised. However, there is lots of progress and new tools (including ex vivo and in vivo models), and there is increased hype that efficient and safe targeted molecular therapies will become successful for several disorders. Here, we are going to highlight the recent advances in Nanomedicine (novel liposomal, polymeric or nanoparticle formulations, etc.) with the hope that they will play a significant role in both improving the quality of life and curing patients.

This Special Issue welcomes original research papers and review articles dealing with the targeted therapeutic delivery of nucleic acids with novel nonviral nanocarriers.

Dr. Aristides D. Tagalakis
Dr. Dimitrios A. Lamprou
Dr. Cynthia Yu-Wai-Man
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 papers will be 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 2200 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

  • gene delivery
  • nanoparticles
  • tumor therapy
  • liposomes
  • polymeric
  • DNA delivery
  • mRNA
  • genome editing
  • cell targeting
  • gene therapy

Published Papers (3 papers)

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Research

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Article
Novel PEGylated Lipid Nanoparticles Have a High Encapsulation Efficiency and Effectively Deliver MRTF-B siRNA in Conjunctival Fibroblasts
Pharmaceutics 2021, 13(3), 382; https://doi.org/10.3390/pharmaceutics13030382 - 13 Mar 2021
Cited by 1 | Viewed by 646
Abstract
The master regulator of the fibrosis cascade is the myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway, making it a key target for anti-fibrotic therapeutics. In the past, inhibitors and small interfering RNAs (siRNAs) targeting the MRTF-B gene have been deployed to counter fibrosis [...] Read more.
The master regulator of the fibrosis cascade is the myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway, making it a key target for anti-fibrotic therapeutics. In the past, inhibitors and small interfering RNAs (siRNAs) targeting the MRTF-B gene have been deployed to counter fibrosis in the eye, with the latter showing promising results. However, the biggest challenge in implementing siRNA therapeutics is the method of delivery. In this study, we utilised the novel, pH-sensitive, cationic lipid CL4H6, which has previously demonstrated potent targeting of hepatocytes and endosomal escape, to safely and efficiently deliver an MRTF-B siRNA into human conjunctival fibroblasts. We prepared two lipid nanoparticle (LNP) formulations, incorporating targeting cleavable peptide cY in one of them, and measured their physicochemical properties and silencing effect in human conjunctival fibroblasts. Both proved to be non-cytotoxic at a concentration of 50 nM and effectively silenced the MRTF-B gene in vitro, with the targeting cleavable peptide not affecting the silencing efficiency [LNP with cY: 62.1% and 81.5% versus LNP without cY: 77.7% and 80.2%, at siRNA concentrations of 50 nM (p = 0.06) and 100 nM (p = 0.09), respectively]. On the other hand, the addition of the targeting cleavable peptide significantly increased the encapsulation efficiency of the LNPs from 92.5% to 99.3% (p = 0.0005). In a 3D fibroblast-populated collagen matrix model, both LNP formulations significantly decreased fibroblast contraction after a single transfection. We conclude that the novel PEGylated CL4H6-MRTF-B siRNA-loaded LNPs represent a promising therapeutic approach to prevent conjunctival fibrosis after glaucoma filtration surgery. Full article
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Article
Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications
Pharmaceutics 2020, 12(12), 1219; https://doi.org/10.3390/pharmaceutics12121219 - 16 Dec 2020
Cited by 2 | Viewed by 1121
Abstract
Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as [...] Read more.
Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as a tool for safe and transient gene delivery. This study assesses MgAl-NO3 layered double hydroxide (LDH) as a nonviral vector to deliver nucleic acids (pDNA, miRNA and siRNA) to mesenchymal stromal cells (MSCs) in 2D culture and using a 3D tissue engineering scaffold approach. Nanoparticles were formulated by complexing LDH with pDNA, microRNA (miRNA) mimics and inhibitors, and siRNA at varying mass ratios of LDH:nucleic acid. In 2D monolayer, pDNA delivery demonstrated significant cytotoxicity issues, and low cellular transfection was deemed to be a result of the poor physicochemical properties of the LDH–pDNA nanoparticles. However, the lower mass ratios required to successfully complex with miRNA and siRNA cargo allowed for efficient delivery to MSCs. Furthermore, incorporation of LDH–miRNA nanoparticles into collagen-nanohydroxyapatite scaffolds resulted in successful overexpression of miRNA in MSCs, demonstrating the development of an efficacious miRNA delivery platform for gene therapy applications in regenerative medicine. Full article
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Review

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Review
Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB
Pharmaceutics 2020, 12(12), 1216; https://doi.org/10.3390/pharmaceutics12121216 - 15 Dec 2020
Cited by 2 | Viewed by 1276
Abstract
The era of the aging society has arrived, and this is accompanied by an increase in the absolute numbers of patients with neurological disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such neurological disorders are serious costly diseases that have a [...] Read more.
The era of the aging society has arrived, and this is accompanied by an increase in the absolute numbers of patients with neurological disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such neurological disorders are serious costly diseases that have a significant impact on society, both globally and socially. Gene therapy has great promise for the treatment of neurological disorders, but only a few gene therapy drugs are currently available. Delivery to the brain is the biggest hurdle in developing new drugs for the central nervous system (CNS) diseases and this is especially true in the case of gene delivery. Nanotechnologies such as viral and non-viral vectors allow efficient brain-targeted gene delivery systems to be created. The purpose of this review is to provide a comprehensive review of the current status of the development of successful drug delivery to the CNS for the treatment of CNS-related disorders especially by gene therapy. We mainly address three aspects of this situation: (1) blood-brain barrier (BBB) functions; (2) adeno-associated viral (AAV) vectors, currently the most advanced gene delivery vector; (3) non-viral brain targeting by non-invasive methods. Full article
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