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Recent Advances of Targeted Drug Delivery and Nanocarriers

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (20 September 2023) | Viewed by 12281

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Special Issue Editors

Dr. Johanna Simon

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Guest Editor

Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr 1, 55131 Mainz, Germany
Interests: targeted drug delivery; nanocarriers

Dr. Michael Fichter

E-Mail Website
Guest Editor

Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Interests: targeted drug delivery; nanocarriers

Special Issue Information

Dear Colleagues,

Nanocarriers hold great promise as delivery systems for various drugs or biomolecules as they can improve the therapeutic efficacy and reduce toxicity. For example, lipid nanoparticles have recently successfully been used for COVID-19 mRNA vaccines.

Depending on the application, nanocarriers are specially designed to deliver the drug to the targeted body region. Both, the nanocarrier’s material and its composition need to be optimized for a specific application.

The most prominent strategy for a targeted delivery of the nanocarrier inside the body is the functionalization of the nanocarrier’s surface with targeting ligands. The attachment of a target ligand (e.g. an antibody) to the surface of nanocarriers allows a site-specific interaction hereby releasing the drug at the targeted cell inside of the body. Nanocarriers with optimized properties are the next generation of drug delivery systems to address current unmet medical needs.

This Special Issue titled “Recent Advances of Targeted Drug Delivery and Nanocarriers” of the International Journal of Molecular Sciences seeks for manuscript submissions that describe novel designed nanocarriers and new strategies for targeted drug delivery. Publications that aim to get a deeper understanding on the development and manufacturing of nanocarriers that allow a controlled and site-specific drug release in vivo are also very welcome.

Dr. Johanna Simon
Dr. Michael Fichter
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

functionalization strategies
site-specific delivery
controlled drug release
nanocarrier design
manufacturing of tailored nanocarriers

Published Papers (6 papers)

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Research

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18 pages, 3727 KiB

Open AccessArticle

Peptide-Decorated Degradable Polycarbonate Nanogels for Eliciting Antigen-Specific Immune Responses

by Judith Stickdorn, Christian Czysch, Carolina Medina-Montano, Lara Stein, Lujuan Xu, Maximilian Scherger, Hansjörg Schild, Stephan Grabbe and Lutz Nuhn

Int. J. Mol. Sci. 2023, 24(20), 15417; https://doi.org/10.3390/ijms242015417 - 21 Oct 2023

Cited by 2 | Viewed by 1414

Abstract

For successful therapeutic interventions in cancer immunotherapy, strong antigen-specific immune responses are required. To this end, immunostimulating cues must be combined with antigens to simultaneously arrive at antigen-presenting cells and initiate cellular immune responses. Recently, imidazoquinolines have shown their vast potential as small molecular Toll-like receptor 7/8 (TLR7/8) agonists for immunostimulation when delivered by nanocarriers. At the same time, peptide antigens are promising antigen candidates but require combination with immune-stimulating adjuvants to boost their immunogenicity and exploit their full potential. Consequently, we herein present biodegradable polycarbonate nanogels as versatile delivery system for adjuvants within the particles’ core as well as for peptide antigens by surface decoration. For that purpose, orthogonally addressable multifunctional polycarbonate block copolymers were synthesized, enabling adjuvant conjugation through reactive ester chemistry and peptide decoration by strain-promoted alkyne-azide cycloaddition (SPAAC). In preparation for SPAAC, CD4⁺-specific peptide sequences of the model protein antigen ovalbumin were equipped with DBCO-moieties by site-selective modification at their N-terminal cysteine. With their azide groups exposed on their surface, the adjuvant-loaded nanogels were then efficiently decorated with DBCO-functional CD4⁺-peptides by SPAAC. In vitro evaluation of the adjuvant-loaded peptide-decorated gels then confirmed their strong immunostimulating properties as well as their high biocompatibility. Despite their covalent conjugation, the CD4⁺-peptide-decorated nanogels led to maturation of primary antigen-presenting cells and the downstream priming of CD4⁺-T cells. Subsequently, the peptide-decorated nanogels loaded with TLR7/8 agonist were successfully processed by antigen-presenting cells, enabling potent immune responses for future application in antigen-specific cancer immunotherapy. Full article

(This article belongs to the Special Issue Recent Advances of Targeted Drug Delivery and Nanocarriers)

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8 pages, 1419 KiB

Open AccessCommunication

Exploring a Nuclear-Selective Radioisotope Delivery System for Efficient Targeted Alpha Therapy

by Yuki Iizuka, Yoshiyuki Manabe, Kazuhiro Ooe, Atsushi Toyoshima, Xiaojie Yin, Hiromitsu Haba, Kazuya Kabayama and Koichi Fukase

Int. J. Mol. Sci. 2023, 24(11), 9593; https://doi.org/10.3390/ijms24119593 - 31 May 2023

Cited by 1 | Viewed by 1435

Abstract

Targeted alpha therapy (TAT) has garnered significant interest as an innovative cancer therapy. Owing to their high energy and short range, achieving selective α-particle accumulation in target tumor cells is crucial for obtaining high potency without adverse effects. To meet this demand, we fabricated an innovative radiolabeled antibody, specifically designed to selectively deliver ²¹¹At (α-particle emitter) to the nuclei of cancer cells. The developed ²¹¹At-labeled antibody exhibited a superior effect compared to its conventional counterparts. This study paves the way for organelle-selective drug delivery. Full article

(This article belongs to the Special Issue Recent Advances of Targeted Drug Delivery and Nanocarriers)

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Review

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30 pages, 1528 KiB

Open AccessReview

Overview of Recent Advances in Nano-Based Ocular Drug Delivery

by Li-Ching Liu, Yi-Hao Chen and Da-Wen Lu

Int. J. Mol. Sci. 2023, 24(20), 15352; https://doi.org/10.3390/ijms242015352 - 19 Oct 2023

Cited by 7 | Viewed by 2328

Abstract

Ocular diseases profoundly impact patients’ vision and overall quality of life globally. However, effective ocular drug delivery presents formidable challenges within clinical pharmacology and biomaterial science, primarily due to the intricate anatomical and physiological barriers unique to the eye. In this comprehensive review, we aim to shed light on the anatomical and physiological features of the eye, emphasizing the natural barriers it presents to drug administration. Our goal is to provide a thorough overview of various characteristics inherent to each nano-based drug delivery system. These encompass nanomicelles, nanoparticles, nanosuspensions, nanoemulsions, microemulsions, nanofibers, dendrimers, liposomes, niosomes, nanowafers, contact lenses, hydrogels, microneedles, and innovative gene therapy approaches employing nano-based ocular delivery techniques. We delve into the biology and methodology of these systems, introducing their clinical applications over the past decade. Furthermore, we discuss the advantages and challenges illuminated by recent studies. While nano-based drug delivery systems for ophthalmic formulations are gaining increasing attention, further research is imperative to address potential safety and toxicity concerns. Full article

(This article belongs to the Special Issue Recent Advances of Targeted Drug Delivery and Nanocarriers)

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19 pages, 3779 KiB

Open AccessReview

Transferrin-Targeted Liposomes in Glioblastoma Therapy: A Review

by Paul Kawak, Nour M. Al Sawaftah, William G. Pitt and Ghaleb A. Husseini

Int. J. Mol. Sci. 2023, 24(17), 13262; https://doi.org/10.3390/ijms241713262 - 26 Aug 2023

Cited by 2 | Viewed by 1462

Abstract

Glioblastoma (GBM) is a highly aggressive brain tumor, and its treatment is further complicated by the high selectivity of the blood–brain barrier (BBB). The scientific community is urgently seeking innovative and effective therapeutic solutions. Liposomes are a promising new tool that has shown potential in addressing the limitations of chemotherapy, such as poor bioavailability and toxicity to healthy cells. However, passive targeting strategies based solely on the physicochemical properties of liposomes have proven ineffective due to a lack of tissue specificity. Accordingly, the upregulation of transferrin receptors (TfRs) in brain tissue has led to the development of TfR-targeted anticancer therapeutics. Currently, one of the most widely adopted methods for improving drug delivery in the treatment of GBM and other neurological disorders is the utilization of active targeting strategies that specifically target this receptor. In this review, we discuss the role of Tf-conjugated liposomes in GBM therapy and present some recent studies investigating the drug delivery efficiency of Tf-liposomes; in addition, we address some challenges currently facing this approach to treatment and present some potential improvement possibilities. Full article

(This article belongs to the Special Issue Recent Advances of Targeted Drug Delivery and Nanocarriers)

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18 pages, 1658 KiB

Open AccessReview

Delivery of Immunostimulatory Cargos in Nanocarriers Enhances Anti-Tumoral Nanovaccine Efficacy

by Jenny Schunke, Volker Mailänder, Katharina Landfester and Michael Fichter

Int. J. Mol. Sci. 2023, 24(15), 12174; https://doi.org/10.3390/ijms241512174 - 29 Jul 2023

Cited by 3 | Viewed by 1561

Abstract

Finding a long-term cure for tumor patients still represents a major challenge. Immunotherapies offer promising therapy options, since they are designed to specifically prime the immune system against the tumor and modulate the immunosuppressive tumor microenvironment. Using nucleic-acid-based vaccines or cellular vaccines often does not achieve sufficient activation of the immune system in clinical trials. Additionally, the rapid degradation of drugs and their non-specific uptake into tissues and cells as well as their severe side effects pose a challenge. The encapsulation of immunomodulatory molecules into nanocarriers provides the opportunity of protected cargo transport and targeted uptake by antigen-presenting cells. In addition, different immunomodulatory cargos can be co-delivered, which enables versatile stimulation of the immune system, enhances anti-tumor immune responses and improves the toxicity profile of conventional chemotherapeutic agents. Full article

(This article belongs to the Special Issue Recent Advances of Targeted Drug Delivery and Nanocarriers)

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23 pages, 1107 KiB

Open AccessReview

Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications

by Leonard Kaps, María José Limeres, Paul Schneider, Malin Svensson, Yanira Zeyn, Silvia Fraude, Maximiliano L. Cacicedo, Peter R. Galle, Stephan Gehring and Matthias Bros

Int. J. Mol. Sci. 2023, 24(14), 11869; https://doi.org/10.3390/ijms241411869 - 24 Jul 2023

Cited by 1 | Viewed by 3353

Abstract

Hepatocytes exert pivotal roles in metabolism, protein synthesis and detoxification. Non-parenchymal liver cells (NPCs), largely comprising macrophages, dendritic cells, hepatic stellate cells and liver sinusoidal cells (LSECs), serve to induce immunological tolerance. Therefore, the liver is an important target for therapeutic approaches, in case of both (inflammatory) metabolic diseases and immunological disorders. This review aims to summarize current preclinical nanodrug-based approaches for the treatment of liver disorders. So far, nano-vaccines that aim to induce hepatitis virus-specific immune responses and nanoformulated adjuvants to overcome the default tolerogenic state of liver NPCs for the treatment of chronic hepatitis have been tested. Moreover, liver cancer may be treated using nanodrugs which specifically target and kill tumor cells. Alternatively, nanodrugs may target and reprogram or deplete immunosuppressive cells of the tumor microenvironment, such as tumor-associated macrophages. Here, combination therapies have been demonstrated to yield synergistic effects. In the case of autoimmune hepatitis and other inflammatory liver diseases, anti-inflammatory agents can be encapsulated into nanoparticles to dampen inflammatory processes specifically in the liver. Finally, the tolerance-promoting activity especially of LSECs has been exploited to induce antigen-specific tolerance for the treatment of allergic and autoimmune diseases. Full article

(This article belongs to the Special Issue Recent Advances of Targeted Drug Delivery and Nanocarriers)

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