Symbiotic Materials for Pharmaceutics

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

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 11355

Special Issue Editors


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Guest Editor
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki-shi, Nagasaki 852-8521, Japan
Interests: nucleic acid drugs; chemistry of functional molecules; exosome; material symbiosis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Research Center for Functional Materials (RCFM), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba 305-0044, Japan
Interests: smart polymers; anti-inflammation; apoptosis; material symbiosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The human body encompasses amazing symbiotic relationships with several organisms, the relationship between a mother and her unborn baby being one such remarkable interaction. The mother does not reject her fetus, even though the fetus is a completely separate organism. In contrast, although research on many different types of functional molecules has been realized, including biological drugs and biocompatible materials, the mechanisms of the symbiosis between humans and non-self molecules/materials is less understood; even highly optimized advanced drugs exhibit immunogenicity in some cases, which has become a major challenge for clinical applications.

In this Special Issue, we refer to the symbiosis between human living cells and materials as “material symbiosis”. We aim to elucidate relationships between biomolecules and materials in terms of biophysical chemistry and review the development of biomaterials that exhibit desired relationships with biomolecules or living cells. We hope this Special Issue will act as an effective design guideline for materials and drugs to avoid conventional side effects, such as immunogenicity and induction of malignancy. To further build upon the collective knowledge in this area, we are inviting reviews and research articles from clinical, academic, and industry settings on “Symbiotic Materials for Pharmaceutics”.

Prof. Dr. Asako Yamayoshi
Prof. Dr. Mitsuhiro Ebara
Guest Editors

Manuscript Submission Information

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Keywords

  • material symbiosis
  • biomaterials
  • biological drugs
  • immunogenicity
  • drug delivery system

Published Papers (5 papers)

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Research

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13 pages, 2802 KiB  
Article
Newly Designed Cysteine-Based Self-Assembling Prodrugs for Sepsis Treatment
by Yuta Koda and Yukio Nagasaki
Pharmaceutics 2023, 15(6), 1775; https://doi.org/10.3390/pharmaceutics15061775 - 20 Jun 2023
Cited by 2 | Viewed by 1227
Abstract
Reactive oxygen species (ROS) are essential signaling molecules that maintain intracellular redox balance; however, the overproduction of ROS often causes dysfunction in redox homeostasis and induces serious diseases. Antioxidants are crucial candidates for reducing overproduced ROS; however, most antioxidants are less effective than [...] Read more.
Reactive oxygen species (ROS) are essential signaling molecules that maintain intracellular redox balance; however, the overproduction of ROS often causes dysfunction in redox homeostasis and induces serious diseases. Antioxidants are crucial candidates for reducing overproduced ROS; however, most antioxidants are less effective than anticipated. Therefore, we designed new polymer-based antioxidants based on the natural amino acid, cysteine (Cys). Amphiphilic block copolymers, composed of a hydrophilic poly(ethylene glycol) (PEG) segment and a hydrophobic poly(cysteine) (PCys) segment, were synthesized. In the PCys segment, the free thiol groups in the side chain were protected by thioester moiety. The obtained block copolymers formed self-assembling nanoparticles (NanoCys(Bu)) in water, and the hydrodynamic diameter was 40–160 nm, as determined by dynamic light scattering (DLS) measurements. NanoCys(Bu) was stable from pH 2 to 8 under aqueous conditions, as confirmed by the hydrodynamic diameter of NanoCys(Bu). Finally, NanoCys(Bu) was applied to sepsis treatment to investigate the potential of NanoCys(Bu). NanoCys(Bu) was supplied to BALB/cA mice by free drinking for two days, and lipopolysaccharide (LPS) was intraperitoneally injected into the mice to prepare a sepsis shock model (LPS = 5 mg per kg body weight (BW)). Compared with the Cys and no-treatment groups, NanoCys(Bu) prolonged the half-life by five to six hours. NanoCys(Bu), designed in this study, shows promise as a candidate for enhancing antioxidative efficacy and mitigating the adverse effect of cysteine. Full article
(This article belongs to the Special Issue Symbiotic Materials for Pharmaceutics)
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10 pages, 2028 KiB  
Communication
Development of Synthetic mRNAs Encoding Split Cytotoxic Proteins for Selective Cell Elimination Based on Specific Protein Detection
by Kendall Free, Hideyuki Nakanishi and Keiji Itaka
Pharmaceutics 2023, 15(1), 213; https://doi.org/10.3390/pharmaceutics15010213 - 7 Jan 2023
Cited by 3 | Viewed by 2045
Abstract
For the selective elimination of deleterious cells (e.g., cancer cells and virus-infected cells), the use of a cytotoxic gene is a promising approach. DNA-based systems have achieved selective cell elimination but risk insertional mutagenesis. Here, we developed a synthetic mRNA-based system to selectively [...] Read more.
For the selective elimination of deleterious cells (e.g., cancer cells and virus-infected cells), the use of a cytotoxic gene is a promising approach. DNA-based systems have achieved selective cell elimination but risk insertional mutagenesis. Here, we developed a synthetic mRNA-based system to selectively eliminate cells expressing a specific target protein. The synthetic mRNAs used in the system are designed to express an engineered protein pair that are based on a cytotoxic protein, Barnase. Each engineered protein is composed of an N- or C-terminal fragment of Barnase, a target protein binding domain, and an intein that aids in reconstituting full-length Barnase from the two fragments. When the mRNAs are transfected to cells expressing the target protein, both N- and C-terminal Barnase fragments bind to the target protein, causing the intein to excise itself and reconstitute cytotoxic full-length Barnase. In contrast, when the target protein is not present, the reconstitution of full-length Barnase is not induced. Four candidate constructs containing split Barnase were evaluated for the ability to selectively eliminate target protein–expressing cells. One of the candidate sets demonstrated highly selective cell death. This system will be a useful therapeutic tool to selectively eliminate deleterious cells. Full article
(This article belongs to the Special Issue Symbiotic Materials for Pharmaceutics)
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15 pages, 2760 KiB  
Article
Flavonoids Enhance Lipofection Efficiency and Ameliorate Cytotoxicity in Colon26 and HepG2 Cells via Oxidative Stress Regulation
by Die Hu, Shintaro Fumoto, Hirotaka Miyamoto, Masakazu Tanaka and Koyo Nishida
Pharmaceutics 2022, 14(6), 1203; https://doi.org/10.3390/pharmaceutics14061203 - 5 Jun 2022
Cited by 2 | Viewed by 1957
Abstract
The generation of reactive oxygen species (ROS) can affect cationic liposome-mediated transfection. In this study, we focused on a specific class of antioxidants, flavonoids, to investigate the transfection efficiency using cationic liposome/plasmid DNA complexes (lipoplexes) in 2D and 3D cultures of Colon26 and [...] Read more.
The generation of reactive oxygen species (ROS) can affect cationic liposome-mediated transfection. In this study, we focused on a specific class of antioxidants, flavonoids, to investigate the transfection efficiency using cationic liposome/plasmid DNA complexes (lipoplexes) in 2D and 3D cultures of Colon26 and HepG2 cells, respectively. All tested flavonoids enhanced the transfection efficiency in 2D Colon26 and HepG2 cells. Among the tested flavonoids, 25 µM quercetin showed the highest promotion effect of 8.4- and 7.6-folds in 2D Colon26 and HepG2 cells, respectively. Transfection was also performed in 3D cultures of Colon26 and HepG2 cells using lipoplexes with quercetin. Quercetin (12.5 µM) showed the highest transfection efficiency at all transfection timings in 3D Colon26 and HepG2 cells with increased cell viability. Flow cytometry revealed that quercetin treatment reduced the population of gene expression-negative cells with high ROS levels and increased the number of gene expression-positive cells with low ROS levels in HepG2 cells. Information from this study can be valuable to develop strategies to promote transfection efficiency and attenuate cytotoxicity using lipoplexes. Full article
(This article belongs to the Special Issue Symbiotic Materials for Pharmaceutics)
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Review

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21 pages, 4185 KiB  
Review
Recent Advancements in Development and Therapeutic Applications of Genome-Targeting Triplex-Forming Oligonucleotides and Peptide Nucleic Acids
by Yu Mikame and Asako Yamayoshi
Pharmaceutics 2023, 15(10), 2515; https://doi.org/10.3390/pharmaceutics15102515 - 23 Oct 2023
Viewed by 1936
Abstract
Recent developments in artificial nucleic acid and drug delivery systems present possibilities for the symbiotic engineering of therapeutic oligonucleotides, such as antisense oligonucleotides (ASOs) and small interfering ribonucleic acids (siRNAs). Employing these technologies, triplex-forming oligonucleotides (TFOs) or peptide nucleic acids (PNAs) can be [...] Read more.
Recent developments in artificial nucleic acid and drug delivery systems present possibilities for the symbiotic engineering of therapeutic oligonucleotides, such as antisense oligonucleotides (ASOs) and small interfering ribonucleic acids (siRNAs). Employing these technologies, triplex-forming oligonucleotides (TFOs) or peptide nucleic acids (PNAs) can be applied to the development of symbiotic genome-targeting tools as well as a new class of oligonucleotide drugs, which offer conceptual advantages over antisense as the antigene target generally comprises two gene copies per cell rather than multiple copies of mRNA that are being continually transcribed. Further, genome editing by TFOs or PNAs induces permanent changes in the pathological genes, thus facilitating the complete cure of diseases. Nuclease-based gene-editing tools, such as zinc fingers, CRISPR-Cas9, and TALENs, are being explored for therapeutic applications, although their potential off-target, cytotoxic, and/or immunogenic effects may hinder their in vivo applications. Therefore, this review is aimed at describing the ongoing progress in TFO and PNA technologies, which can be symbiotic genome-targeting tools that will cause a near-future paradigm shift in drug development. Full article
(This article belongs to the Special Issue Symbiotic Materials for Pharmaceutics)
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14 pages, 2696 KiB  
Review
Chemistry of Therapeutic Oligonucleotides That Drives Interactions with Biomolecules
by Chisato Terada, Seiya Kawamoto, Asako Yamayoshi and Tsuyoshi Yamamoto
Pharmaceutics 2022, 14(12), 2647; https://doi.org/10.3390/pharmaceutics14122647 - 29 Nov 2022
Cited by 3 | Viewed by 2804
Abstract
Oligonucleotide therapeutics that can modulate gene expression have been gradually developed for clinical applications over several decades. However, rapid advances have been made in recent years. Artificial nucleic acid technology has overcome many challenges, such as (1) poor target affinity and selectivity, (2) [...] Read more.
Oligonucleotide therapeutics that can modulate gene expression have been gradually developed for clinical applications over several decades. However, rapid advances have been made in recent years. Artificial nucleic acid technology has overcome many challenges, such as (1) poor target affinity and selectivity, (2) low in vivo stability, and (3) classical side effects, such as immune responses; thus, its application in a wide range of disorders has been extensively examined. However, even highly optimized oligonucleotides exhibit side effects, which limits the general use of this class of agents. In this review, we discuss the physicochemical characteristics that aid interactions between drugs and molecules that belong to living organisms. By systematically organizing the related data, we hope to explore avenues for symbiotic engineering of oligonucleotide therapeutics that will result in more effective and safer drugs. Full article
(This article belongs to the Special Issue Symbiotic Materials for Pharmaceutics)
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