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Pharmaceutics
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Nucleic-Acid-Based Strategies and Nanotechnology Applications for Targeted Therapy, 2nd Edition
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Nucleic-Acid-Based Strategies and Nanotechnology Applications for Targeted Therapy, 2nd Edition

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

Deadline for manuscript submissions: 30 November 2026 | Viewed by 3231

Special Issue Editor

Dr. Andrea Patrizia Falanga

E-Mail Website
Guest Editor
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy
Interests: peptide nucleic acid; G-quadruplex; delivery; solid-phase synthesis; small molecule-DNA interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Due to the recent attention and growing potential that nucleic acids have gained, together with the demand for improving current controlled-release systems, we are pleased to announce this Special Issue, entitled “Nucleic-Acid-Based Strategies and Nanotechnology Applications for Targeted Therapy, 2nd Edition”. The purpose of this Special Issue is to collate papers reporting on, but not limited to, oligonucleotide synthesis, biochemical and biophysical characterization of nucleic acids, new oligonucleotide-based delivery systems, and biomaterial and polymer development. Articles embracing originality and novelty are welcome to be submitted to this Special Issue. We look forward to receiving your contributions.

Dr. Andrea Patrizia Falanga
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 250 words) can be sent to the Editorial Office for assessment.

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

  • nucleic acids
  • drug delivery
  • nanomedicine
  • biotechnology
  • material science

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Related Special Issue

Published Papers (3 papers)

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Research

18 pages, 2367 KB  
Article
CD25-Targeted Aptamer–Drug Conjugate for the Treatment of CD25-Expressing Hematological Malignancies
by Sanghyeok Woo, Ju-Hyung Kang, Inu Song, Soryong Lim, Hwarim Ryu, Yujin Lee and Daekyun Lee
Pharmaceutics 2026, 18(2), 217; https://doi.org/10.3390/pharmaceutics18020217 - 9 Feb 2026
Viewed by 888
Abstract
Background: CD25, the α-chain of the interleukin-2 (IL-2) receptor, is highly expressed on malignant cells and tumor-infiltrating regulatory T-cells (Tregs) in hematologic malignancies, making it an attractive therapeutic target for tumor elimination and immunomodulation. Methods: We developed a CD25-specific aptamer–drug conjugate [...] Read more.
Background: CD25, the α-chain of the interleukin-2 (IL-2) receptor, is highly expressed on malignant cells and tumor-infiltrating regulatory T-cells (Tregs) in hematologic malignancies, making it an attractive therapeutic target for tumor elimination and immunomodulation. Methods: We developed a CD25-specific aptamer–drug conjugate (CD25-ApDC) by linking a CD25 aptamer to monomethyl auristatin E via a cathepsin B-cleavable Val-Cit linker. Results: The aptamer exhibited high affinity for CD25 (Kd = 16.4 ± 0.29 nM), rapid receptor-mediated uptake (half-time = 9.6 min), and selective inhibition of IL-2 signaling in CD25high cells, with no activity in CD25low cells. In vitro, CD25-ApDC induced selective cytotoxicity, confirmed by apoptosis and G2/M arrest in CD25-positive cancer cells while having no effect on CD25-negative cells. Co-culture studies confirmed selective depletion of CD25high Treg-like cells, suggesting potential to relieve immune suppression within the tumor microenvironment. In vivo, CD25-ApDC achieved complete tumor remission in xenograft and disseminated models with optimized dosing, showing efficacy and tolerability comparable to Brentuximab vedotin. Increasing drug-to-aptamer ratios further enhanced outcomes, supporting flexible dosing strategies. Conclusions: These findings highlight CD25-ApDC as a promising therapeutic modality for hematologic malignancies, offering advantages in specificity, tissue penetration, and manufacturability over conventional antibody-based therapies. Full article
(This article belongs to the Special Issue Nucleic-Acid-Based Strategies and Nanotechnology Applications for Targeted Therapy, 2nd Edition)
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19 pages, 4836 KB  
Article
Robust Functionality and Regulation of Selectively Expressed RNA as AAV Vectors and In Vitro Transcribed Molecules
by Frederik Rastfeld, Nils Hersch, Georg Dreissen, Hajaani Manoharan, Laura Wagner, Lukas Lövenich, Elke Barczak, Hildegard Büning, Rudolf Merkel and Bernd Hoffmann
Pharmaceutics 2025, 17(12), 1595; https://doi.org/10.3390/pharmaceutics17121595 - 10 Dec 2025
Viewed by 859
Abstract
Background/Objectives: Selectively expressible RNA (seRNA) molecules represent a promising new platform for the induction of cell type-specific protein expression. Based on the sense–antisense interaction of the seRNA antisense domain with target cell-specific RNA molecules, the partial degradation of the seRNA molecule induces the [...] Read more.
Background/Objectives: Selectively expressible RNA (seRNA) molecules represent a promising new platform for the induction of cell type-specific protein expression. Based on the sense–antisense interaction of the seRNA antisense domain with target cell-specific RNA molecules, the partial degradation of the seRNA molecule induces the activation of an internal ribosomal entry site to initiate translation. The selective expression of seRNA encoded proteins exclusively in target cells works both in vitro and in vivo but is associated with a lower expression intensity compared with classical mRNAs. Furthermore, seRNAs have so far been transfected into cells by plasmid-encoded seRNA expression systems, which is limiting their broad medical applicability. Here, we focus on the characterization of plasmid-based seRNA uptake and activation as well as on options to transfer the seRNA technology to additional vector systems to increase target cell-specific effector expression. Methods: seRNA constructs were generated as expression plasmids, AAV, DNA minicircles and IVT-RNA and delivered into different eukaryotic cell lines by transfection/transduction. Analyses were performed using fluorescence microscopy and, for quantitative analyses, flow cytometry. RNA stability and expression analyses were performed using qRT-PCR. Results: We show that seRNA-based plasmid systems are efficiently transfected into cells but that reduced RNA steady-state levels are present compared with control expression plasmids. This effect is most likely based on reduced transcription efficiency rather than seRNA stability. Furthermore, seRNA transcription from viral vectors or circular DNA significantly increased the effector expression of seRNAs and enabled linear expression regulation while maintaining target cell-specific activation and inactivation in non-target cells. Optimal results were achieved by adapting the technology to in vitro transcribed seRNA. Conclusions: Our data show that seRNA technology develops its full functionality regardless of the type of transfer vector used. Furthermore, expression strength can be regulated within a wide range while maintaining consistent functionality which will enable broad applicability in medicine in the future. Full article
(This article belongs to the Special Issue Nucleic-Acid-Based Strategies and Nanotechnology Applications for Targeted Therapy, 2nd Edition)
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22 pages, 4984 KB  
Article
The Aptamer bi-(AID-1-T) Synergizes with Radiation to Inhibit Proliferation of Human Glioma Cells
by Svetlana Pavlova, Ksenia Rubetskaya, Lika Fab, Ekaterina Savchenko, Nadezhda Samoylenkova, Alexander Revishchin, Anastasia Ryabova, Natalia Antipina, Mikhail Galkin, Andrey Golanov, Dmitry Usachev, Alexey Kopylov and Galina Pavlova
Pharmaceutics 2025, 17(11), 1442; https://doi.org/10.3390/pharmaceutics17111442 - 8 Nov 2025
Cited by 1 | Viewed by 1136
Abstract
Background: High-grade gliomas are treatment-resistant and prone to aggressive recurrence. Although radiation therapy is a fundamental treatment, it often fails to eradicate tumors and can enhance the migratory potential of surviving cells, promoting relapse. Anti-proliferative aptamers are novel agents that show promise, but [...] Read more.
Background: High-grade gliomas are treatment-resistant and prone to aggressive recurrence. Although radiation therapy is a fundamental treatment, it often fails to eradicate tumors and can enhance the migratory potential of surviving cells, promoting relapse. Anti-proliferative aptamers are novel agents that show promise, but their combination with radiation therapy and their effects on invasive phenotypes require further investigation. Objectives: This study evaluated the effects of ionizing radiation on the viability and migration of human glioma cells, both alone and in combination with the anti-proliferative aptamer bi-(AID-1-T). The study aimed to determine whether the aptamer could enhance the efficacy of radiotherapy and counteract ionizing radiation-induced pro-migratory effects. Methods: The study was conducted on cell cultures of primary and relapsed human glioma. The effects of combined radiation (single dose of 20 Gy) and the bi-(AID-1-T) aptamer (10 μM) were assessed using the MTS assay, Transwell analysis, immunocytochemistry and transcriptome analysis. Results: Ionizing radiation alone reduced proliferation in primary gliomas, but increased proliferation in recurrent cultures. Ionizing radiation also increased migration in both types of gliomas. Combining ionizing radiation with the bi-(AID-1-T) aptamer produced a synergistic effect: it significantly reduced cell proliferation and migration, and suppressed the ionizing radiation-induced migratory enhancement, more effectively than either treatment alone. Transcriptome analysis revealed that combination treatment decreased the expression of pro-proliferative and migratory genes (e.g., PDPN, CDH3), while increasing the expression of anti-migratory (RND3) and pro-apoptotic genes (e.g., XAF1, SEMA3A). Thus, combination treatment significantly reduces tumor cell proliferation and migration; however, further studies on surviving cells are needed. Full article
(This article belongs to the Special Issue Nucleic-Acid-Based Strategies and Nanotechnology Applications for Targeted Therapy, 2nd Edition)
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