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Targeted Drug Delivery
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Targeted Drug Delivery

A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".

Deadline for manuscript submissions: closed (1 December 2021) | Viewed by 27443

Special Issue Editors

Dr. António Paulo

E-Mail Website
Guest Editor
C2TN- Centro de Ciências e Tecnologias Nucleares and DECN - Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
Interests: inorganic chemistry; medicinal chemistry; radiopharmaceutical chemistry; nuclear medicine; nanomedicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Paula Campello

E-Mail Website
Guest Editor
Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal

Special Issue Information

Dear Colleagues,

Targeted drug delivery is an advanced method of delivering drugs to patients aiming at increasing the drug’s concentration only in the targeted body part of interest, therefore improving the efficacy of treatment with a reduction of side effects. For this reason, the study of targeted drug delivery systems is under high consideration of research and development in the clinical and pharmaceutical fields.

There are two types of targeted drug delivery: Passive targeting and Active targeting. In both cases, various drug carriers can be used that should be able to cross biological barriers, like the blood brain barrier (BBB) or tumor vasculature in the case of antitumor therapies. Moreover, the drug–carrier complex must be recognized by the target cells specifically and selectively, while being stable in plasma, interstitial liquid, and other biofluids. It should also be biodegradable or readily eliminated from the body without toxic effects, and capable of releasing the drug payload in the target cells, namely, by enzymatic cleavage of appropriate linkers under physiological conditions. The design of suitable carriers that fulfill these requisites for the delivery of different types of drugs (e.g., small organic molecules as cytotoxic agents, metal-based chemotherapeutics, therapeutic antibodies and their fragments) is a quite challenging task and remains a topic of utmost importance in contemporary medicinal chemistry.

This Special Issue of Materials is open to papers focusing on recent developments in the field of targeted drug delivery, either for nanometric (e.g., liposomes, micelles, inorganic nanoparticles, virus like particles, artificial cells) or molecular (antibodies and their fragments, penetrating peptides, etc.) carriers. Contributions reporting image-guided approaches of targeted drug delivery are also welcome. Our intention is to awaken the material science, chemistry, and biology communities to the role of targeted drug delivery systems in the rise of molecular and personalized medicine. Thus, we would be very glad if you consider contributing to this issue by submitting an article (review, research paper, or communication) in one of the topics mentioned above. We are certain your contribution will be inspiring to other scientists engaged in this flourishing field, which will most definitely contribute to the development of more efficient and more selective anticancer therapies in the years to come.

Prof. Dr. António Paulo
Prof. Dr. Paula Campello
Guest Editors

Manuscript Submission Information

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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. Materials is an international peer-reviewed open access semimonthly 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 2600 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

  • Targeted drug delivery
  • Image-guided drug delivery
  • Nanoparticles
  • Antibody–drug conjugates (ADC)
  • Cytotoxic drugs
  • Metal-based chemotherapeutics
  • Therapeutic antibodies

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Published Papers (6 papers)

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Research

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20 pages, 3722 KiB  
Article
Poly-Lysine Dendritic Nanocarrier to Target Epidermal Growth Factor Receptor Overexpressed Breast Cancer for Methotrexate Delivery
by Pratibha Narayanan, Anju Krishnan Anitha, Neethu Ajayakumar and Kesavakurup Santhosh Kumar
Materials 2022, 15(3), 800; https://doi.org/10.3390/ma15030800 - 21 Jan 2022
Cited by 9 | Viewed by 2507
Abstract
A fourth generation poly-lysine dendritic nanocarrier (P4LDN)-based targeted chemotherapy for breast cancer is attempted by incorporating an epidermal growth factor receptor (EGFR)-specific short peptide E2 (ARSHVGYTGAR) and the drug methotrexate (MTX) into a nanocarrier system. The drug is incorporated into the [...] Read more.
A fourth generation poly-lysine dendritic nanocarrier (P4LDN)-based targeted chemotherapy for breast cancer is attempted by incorporating an epidermal growth factor receptor (EGFR)-specific short peptide E2 (ARSHVGYTGAR) and the drug methotrexate (MTX) into a nanocarrier system. The drug is incorporated into the nanocarrier using a cathepsin B cleavable spacer: glycine–phenylalanine–leucine–glycine (GFLG). The in vitro analysis of the time-dependent drug release, binding and internalization ability, and the cytotoxic nature showed that this drug delivery system (DDS) is highly effective. The efficacy analysis using non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice also showed that compared to the control group, the DDS can effectively reduce tumor volume. The mice that received the DDS appeared to gain weight more rapidly than the free drug, which suggests that the dendrimer is more easily tolerated by mice than the free drug. Full article
(This article belongs to the Special Issue Targeted Drug Delivery)
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18 pages, 4427 KiB  
Article
Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells
by Ju-Il Yang, Hye-Lim Lee, Seon-Hee Choi, Jungsoo Kim, Young-Bob Yu, Young-IL Jeong and Dae-Hwan Kang
Materials 2022, 15(1), 138; https://doi.org/10.3390/ma15010138 - 25 Dec 2021
Cited by 2 | Viewed by 2745
Abstract
The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 [...] Read more.
The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 was conjugated with mPEG via selenocystamine linkage and then remaining carboxylic acid groups of Ce6 was attached to PBAP (mPEGseseCe6PBAP conjugates). Nanophotosensitizers of mPEGseseCe6PBAP conjugates were prepared by dialysis method. In transmission electron microscope (TEM) observation, nanophotosensitizers of mPEGseseCe6PBAP conjugates have spherical shapes and their diameters were less than 150 nm. The average diameter of mPEGseseCe6PBAP nanophotosensitizers was 92.7 ± 9.6 nm in particle size analysis. When H2O2 was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H2O2 concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H2O2 concentration. When H2O2 was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H2O2 concentration, indicating that nanophotosensitizers showed ROS-sensitive delivery of Ce6 against cancer cells.As well as free Ce6, nanophotosensitizers in the absence of light irradiation have low intrinsic cytotoxicity against RAW264.7 cells and HeLa cells. However, nanophotosensitizers induced cell death dose-dependently under light irradiation. Especially, nanophotosensitizers showed significantly higher ROS generation and phototoxicity against HeLa cells in vitro. When nanophotosensitizers were intravenously administered to animal tumor xenograft model of HeLa cells, tumor tissues revealed stronger fluorescence intensity than other tissues by light irradiation while absence of light irradiation induced relatively lower fluorescence intensity in tumor tissues, indicating that nanophotosensitizers have sensitivity against oxidative stress in tumor tissues. We suggest that nanophotosensitizers of mPEGseseCe6PBAP conjugates are promising vehicle for PDT of cervical cancer cells. Full article
(This article belongs to the Special Issue Targeted Drug Delivery)
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17 pages, 1690 KiB  
Article
Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics
by Francisco Silva, António Paulo, Agnès Pallier, Sandra Même, Éva Tóth, Lurdes Gano, Fernanda Marques, Carlos F.G.C. Geraldes, M. Margarida C.A. Castro, Ana M. Cardoso, Amália S. Jurado, Pilar López-Larrubia, Sara Lacerda and Maria Paula Cabral Campello
Materials 2020, 13(3), 513; https://doi.org/10.3390/ma13030513 - 22 Jan 2020
Cited by 20 | Viewed by 4570
Abstract
Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for [...] Read more.
Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with affinity towards the gastrin releasing peptide receptor (GRPr), overexpressed in a variety of human cancer cells, namely PC3 prostate cancer cells. The potential of these multimodal imaging nanoconstructs was thoroughly investigated by the assessment of their magnetic properties, in vitro cellular uptake, biodistribution, and radiosensitisation assays. The relaxometric properties predict a potential T1- and T2- MRI application. The promising in vitro cellular uptake of 67Ga/Gd-based bombesin containing particles was confirmed through biodistribution studies in tumor bearing mice, indicating their integrity and ability to target the GRPr. Radiosensitization studies revealed the therapeutic potential of the nanoparticles. Moreover, the DOTA chelating unit moiety versatility gives a high theranostic potential through the coordination of other therapeutically interesting radiometals. Altogether, our nanoparticles are interesting nanomaterial for theranostic application and as bimodal T1- and T2- MRI / SPECT imaging probes. Full article
(This article belongs to the Special Issue Targeted Drug Delivery)
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Review

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15 pages, 4497 KiB  
Review
Electrochemotherapy and Other Clinical Applications of Electroporation for the Targeted Therapy of Metastatic Melanoma
by Corina Ioana Cucu, Călin Giurcăneanu, Liliana Gabriela Popa, Olguța Anca Orzan, Cristina Beiu, Alina Maria Holban, Alexandru Mihai Grumezescu, Bogdan Mircea Matei, Marius Nicolae Popescu, Constantin Căruntu and Mara Mădălina Mihai
Materials 2021, 14(14), 3985; https://doi.org/10.3390/ma14143985 - 16 Jul 2021
Cited by 6 | Viewed by 4337
Abstract
Electrochemotherapy (ECT) is an effective bioelectrochemical procedure that uses controlled electrical pulses to facilitate the increase of intracellular concentration of certain substances (electropermeabilization/ reversible electroporation). ECT using antitumor drugs such as bleomycin and cisplatin is a minimally invasive targeted therapy that can be [...] Read more.
Electrochemotherapy (ECT) is an effective bioelectrochemical procedure that uses controlled electrical pulses to facilitate the increase of intracellular concentration of certain substances (electropermeabilization/ reversible electroporation). ECT using antitumor drugs such as bleomycin and cisplatin is a minimally invasive targeted therapy that can be used as an alternative for oncologic patients not eligible for surgery or other standard therapies. Even though ECT is mainly applied as palliative care for metastases, it may also be used for primary tumors that are unresectable due to size and location. Skin neoplasms are the main clinical indication of ECT, the procedure reporting good curative results and high efficiency across all tumor types, including melanoma. In daily practice, there are many cases in which the patient’s quality of life can be significantly improved by a safe procedure such as ECT. Its popularity must be increased because it has a safe profile and minor local adverse reactions. The method can be used by dermatologists, oncologists, and surgeons. The aim of this paper is to review recent literature concerning electrochemotherapy and other clinical applications of electroporation for the targeted therapy of metastatic melanoma. Full article
(This article belongs to the Special Issue Targeted Drug Delivery)
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32 pages, 2793 KiB  
Review
Radiolabeled Gold Nanoparticles for Imaging and Therapy of Cancer
by Francisco Silva, Maria Paula Cabral Campello and António Paulo
Materials 2021, 14(1), 4; https://doi.org/10.3390/ma14010004 - 22 Dec 2020
Cited by 41 | Viewed by 5938
Abstract
In the Last decades, nanotechnology has provided novel and alternative methodologies and tools in the field of medical oncology, in order to tackle the issues regarding the control and treatment of cancer in modern society. In particular, the use of gold nanoparticles (AuNPs) [...] Read more.
In the Last decades, nanotechnology has provided novel and alternative methodologies and tools in the field of medical oncology, in order to tackle the issues regarding the control and treatment of cancer in modern society. In particular, the use of gold nanoparticles (AuNPs) in radiopharmaceutical development has provided various nanometric platforms for the delivery of medically relevant radioisotopes for SPECT/PET diagnosis and/or radionuclide therapy. In this review, we intend to provide insight on the methodologies used to obtain and characterize radiolabeled AuNPs while reporting relevant examples of AuNPs developed during the last decade for applications in nuclear imaging and/or radionuclide therapy, and highlighting the most significant preclinical studies and results. Full article
(This article belongs to the Special Issue Targeted Drug Delivery)
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20 pages, 6620 KiB  
Review
Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems
by Claudia Sandoval-Yañez and Cristian Castro Rodriguez
Materials 2020, 13(3), 570; https://doi.org/10.3390/ma13030570 - 24 Jan 2020
Cited by 97 | Viewed by 5767
Abstract
Today, dendrimers are the main nanoparticle applied to drug delivery systems. The physicochemical characteristics of dendrimers and their versatility structural modification make them attractive to applied as a platform to bioactive molecules transport. Nanoformulations based on dendrimers enhance low solubility drugs, arrival to [...] Read more.
Today, dendrimers are the main nanoparticle applied to drug delivery systems. The physicochemical characteristics of dendrimers and their versatility structural modification make them attractive to applied as a platform to bioactive molecules transport. Nanoformulations based on dendrimers enhance low solubility drugs, arrival to the target tissue, drugs bioavailability, and controlled release. This review describes the latter approaches on the transport of bioactive molecules based on dendrimers. The review focus is on the last therapeutic strategies addressed by dendrimers conjugated with bioactive molecules. A brief review of the latest studies in therapies against cancer and cardiovascular diseases, as well as future projections in the area, are addressed. Full article
(This article belongs to the Special Issue Targeted Drug Delivery)
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