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Pharmaceutics
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A New Generation of Metal Anticancer Drugs
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A New Generation of Metal Anticancer Drugs

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2434

Special Issue Editor

Dr. Ignacio E. León

E-Mail Website
Guest Editor
CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina
Interests: nanoparticles; drug delivery; metallodrugs; medicinal chemistry; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will explore the latest advancements in the design and development of new metal-based anticancer drugs and studies on their mechanism of actions and the structure–activity relationship, focusing on optimizing therapeutic potential while minimizing toxicity. Metal-containing compounds, such as platinum-based drugs (e.g., cisplatin) and emerging metal complexes, have shown promise in cancer treatment, but their chemoresistance and side effects often pose challenges. In the design of novel metallodrugs, it is vital that problems related to bioavailability, stability, resistance, and side effects are addressed. This Special Issue will delve into novel drug delivery systems, including nanoparticles, liposomes, solid lipid nanoparticles, and conjugated formulations, which enhance the solubility, targeting specificity, and controlled release of metal-based agents. Additionally, it will address the pharmacokinetics and pharmacodynamics of metal-based drugs, highlighting strategies for improving their tissue distribution and tumor accumulation. Researchers and pharmaceutical scientists are invited to contribute insights into the formulation design, formulation characterization, and clinical translation of metal-based anticancer therapies, with the aim of providing safer and more effective treatment options for cancer patients.

Dr. Ignacio E. León
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

  • metal-based drugs
  • cytotoxicity
  • cancer
  • nanoparticles
  • drug delivery

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Published Papers (2 papers)

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Research

19 pages, 4669 KB  
Article
In Vitro and In Vivo Effects of a Copper(II)-Hydrazone Complex Against Human Osteosarcoma
by Lucía Santa Maria de la Parra, Matías H. Assandri, Luisina M. Solernó, María de los A. Serradell, Daniel F. Alonso, Juan Garona, Lucía M. Balsa and Ignacio E. León
Pharmaceutics 2026, 18(3), 372; https://doi.org/10.3390/pharmaceutics18030372 - 17 Mar 2026
Viewed by 998
Abstract
Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults, with poor prognosis due to relapse, metastasis, and chemoresistance. The search for novel metal-based therapeutics has highlighted copper complexes as promising candidates. Here, we report the in [...] Read more.
Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults, with poor prognosis due to relapse, metastasis, and chemoresistance. The search for novel metal-based therapeutics has highlighted copper complexes as promising candidates. Here, we report the in vitro and in vivo antitumor activity of a tetranuclear Cu(II)-hydrazone complex (Cu4L4) derived from (E)-5-chloro-N′-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide. Results: Cytotoxic assays on MG-63 OS cells revealed potent activity with an IC50 of 0.50 ± 0.04 µM, significantly surpassing its free ligand (IC50 = 13.9 ± 1.6 µM) and cisplatin (IC50 = 39.0 ± 1.8 µM). This tetranuclear complex outperforms mononuclear Cu-hydrazones analogs (e.g., 4-fold vs. CuHL1, 2-fold vs. CuHL2, 5-fold vs. CuHL3, 17-fold vs. CuHL4,), and Cu4L4 also exhibits reduced clonogenic survival, induces reactive oxygen species production, and promotes late apoptosis as a main mechanism, being the main mechanism of action involved in anticancer activity. In multicellular tumor spheroids, the complex maintained strong cytotoxicity (IC50 = 4.11 ± 0.12 µM), impaired spheroid integrity, and markedly inhibited cell migration at sub-IC50 concentrations. The tetranuclear architecture confers markedly enhanced antitumor activity relative to the corresponding mononuclear Cu–hydrazone complexes (e.g., 2-fold vs. CuHL1, 4-fold vs. CuHL2, 2-fold vs. CuHL3). In a xenograft model, sustained administration of Cu4L4 (2 mg/kg, i.p., twice weekly) inhibited tumor growth by 43.6%, reduced mitotic index, and increased necrotic area without significant systemic toxicity. Conclusions: Overall, Cu4L4 displayed potent and selective antitumor activity against OS cells in 2D, 3D, and in vivo models, underscoring copper–hydrazone complexes as promising scaffolds for the development of new therapies against OS. Full article
(This article belongs to the Special Issue A New Generation of Metal Anticancer Drugs)
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21 pages, 3462 KB  
Article
Fe/57Fe-Metallacarboranes with Radiosensitizing Potential in Breast Cancer Cell Models: Comparative Study Between High- (60Co) and Low-Energy (57Co) Gamma Radiation Sources
by Salvatore Di Maria, Diogo M. Engrácia, Catarina I. G. Pinto, João C. Waerenborgh, Bruno J. C. Vieira, Pedro Santos, Teresa Pinheiro, Miquel Nuez-Martínez, António P. Matos, Filipa Mendes, Francesc Teixidor, Clara Viñas and Fernanda Marques
Pharmaceutics 2026, 18(2), 214; https://doi.org/10.3390/pharmaceutics18020214 - 9 Feb 2026
Viewed by 868
Abstract
Background: Radiosensitizers can be used to enhance tumor response and mitigate toxicity in healthy tissues during radiation therapy. This study investigates the radiosensitizing potential of the metallacarborane Fe/57Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose [...] Read more.
Background: Radiosensitizers can be used to enhance tumor response and mitigate toxicity in healthy tissues during radiation therapy. This study investigates the radiosensitizing potential of the metallacarborane Fe/57Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose 60Co (2.08 Gy) and low-dose 57Co (37.55 mGy, 57Fe Mössbauer effect). Methods: We evaluated cell viability and survival in 2D monolayer and 3D spheroid cultures, as well as the mechanism of cell death (ROS production, apoptosis or necrosis). Computational dosimetry was used to calculate the average absorbed dose. Results: In 2D models, both radiation sources induced reduced viability and increased ROS, with distinct cell death patterns dependent on the source (apoptosis or necrosis). Comparing 2D and 3D MDA-MB-231 models revealed that spheroid survival was significantly more impaired. The low-dose 57Co source caused a significant radiosensitization in MDA-MB-231 spheroids, dramatically impacting viability and survival. This effect is attributed to the Mössbauer effect, where the resonant absorption of 14.41 keV radiation by 57Fe leads to a massive, localized dose enhancement. The subsequent cascade of Auger and conversion electrons (local high LET) caused significantly greater cellular damage than sparse photon radiation. Conclusions: Fe/57Fe-ferrabisdicarbollide demonstrates a potent radiosensitizing effect depending on the cell model and the radiation source used. Crucially, the observed radiosensitization allows for the development of a new, more efficient cancer radiotherapy approach that can achieve therapeutic efficacy using a significantly lower radiation dose to the patient. This paves the way for safer and better-tolerated cancer treatments. Full article
(This article belongs to the Special Issue A New Generation of Metal Anticancer Drugs)
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