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Pharmaceuticals
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Tumor Therapy and Drug Delivery
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Tumor Therapy and Drug Delivery

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 25 October 2025 | Viewed by 11045

Special Issue Editor

Dr. Rositsa Mihaylova

E-Mail Website
Guest Editor
Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria
Interests: antitumor therapy; drug delivery; nanocarriers; tumor resistance models; metal complexes; lipid-based nanoparticles; liposomes; niosomes; natural antitumor compounds; neuroprotection; neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Undoubtedly, the most attractive approach to modulate drug behavior in vivo is technological. The development and implementation of various drug delivery systems with tunable characteristics and release profiles (e.g., the incorporation of active substance into nanocarriers such as liposomes, niosomes, micelles, polymeric nanoparticles, supramolecular composites, etc.) increases the therapeutic index of many antitumor agents and significantly reduces the occurrence and intensity of their dose-limiting toxicities. Furthermore, molecular encapsulation appears to be a viable approach to enhance the selectivity of antitumor agents by providing mechanistic protection from side interactions with tissue components, xenobiotic efflux transporters, biotransforming enzymes and other biomolecules; moreover, it provides broad opportunities for active and/or passive tumor targeting. Thus, the pharmacokinetic behavior of a cargo drug obeys the distribution and elimination patterns of its carrier, thereby resulting in improved penetration and preferential accumulation in malignant cells. The further development and refinement of drug carrier systems that have excellent biocompatibility, biodegradability and targeting properties are not only a major facet of personalized medicine but have also contributed to the resurgence and reinforcement of conventional chemotherapeutics with unfavorable physicochemical or safety profiles. Accordingly, cutting-edge treatment comprises cancer immunotherapy with antibody–drug conjugates designed to provide the active targeting of highly toxic substances to tumor cells expressing specific antigens, thus maximizing the selective tumor delivery of the loaded drug.

The aim of this current Special Issue is to provide a fresh overview of current and future trends in the field of antitumor therapy and drug delivery, highlighting the molecular aspects and potential advantages and challenges of different approaches.

Dr. Rositsa Mihaylova
Guest Editor

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. Pharmaceuticals 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

  • antitumor therapy
  • drug delivery systems
  • nanocarriers
  • immunoconjugates
  • nanotechnology
  • cancer selectivity

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Published Papers (6 papers)

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Research

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40 pages, 9219 KiB  
Article
Enhanced Intranasal Delivery of Atorvastatin via Superparamagnetic Iron-Oxide-Loaded Nanocarriers: Cytotoxicity and Inflammation Evaluation and In Vivo, In Silico, and Network Pharmacology Study for Targeting Glioblastoma Management
by Kristina Zarif Attalla, Doaa H. Hassan, Mahmoud H. Teaima, Carol Yousry, Mohamed A. El-Nabarawi, Mohamed A. Said and Sammar Fathy Elhabal
Pharmaceuticals 2025, 18(3), 421; https://doi.org/10.3390/ph18030421 - 16 Mar 2025
Cited by 8 | Viewed by 1498
Abstract
Objective: This study aims to develop an intranasal (IN) delivery system for glioblastoma multiforme (GBM) management using repurposed superparamagnetic iron-oxide (SPION) loaded with atorvastatin (ATO)-nanostructured lipid carrier (NLC). Methods: Emulsification and ultrasonication were used to formulate ATO-NLCs, and the best formula [...] Read more.
Objective: This study aims to develop an intranasal (IN) delivery system for glioblastoma multiforme (GBM) management using repurposed superparamagnetic iron-oxide (SPION) loaded with atorvastatin (ATO)-nanostructured lipid carrier (NLC). Methods: Emulsification and ultrasonication were used to formulate ATO-NLCs, and the best formula was loaded with SPION to make the final atorvastatin/superparamagnetic iron oxide-loaded nanostructured lipid carrier (ASN) formulation. Entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and drug release after 6 h (Q6h) were evaluated for NLCs. ASN was tested for cytotoxicity on T98G cancer cells, and the cell cycle was examined to determine cell death. Furthermore, the ability of the optimal formulation to suppress the levels of inflammatory biomarkers was investigated in Lipopolysaccharide (LPS)-induced inflammation. The brain-targeting behavior of IN-ASN was visualized in rabbits via confocal laser scanning microscopy (CLSM). Results: The optimum NLC exhibited a spherical shape, EE% of 84.0 ± 0.67%, PS of 282.50 ± 0.51 nm, ZP of −18.40 ± 0.15 mV, and Q6h of 89.23%. The cytotoxicity of ASN against cancer cells was 4.4-fold higher than ATO suspension, with a 1.3-fold increment in cell apoptosis. ASN showed significantly reduced pro-inflammatory biomarkers (IL-β, IL-6, TNF-α, TLR4, NF-қB), whereas CLSM revealed enhanced brain delivery with no observed histopathological nasal irritation. The in silico analysis demonstrated enhanced ATO-ADME (absorption, distribution, metabolism, and excretion) properties, while the network pharmacology study identified 10 target GBM genes, among which MAPK3 was the most prominent with a good binding score as elucidated by the simulated docking study. Conclusions: These findings may present ATO/SPION-NLCs as significant evidence for repurposing atorvastatin in the treatment of glioblastoma multiforme. Full article
(This article belongs to the Special Issue Tumor Therapy and Drug Delivery)
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17 pages, 6883 KiB  
Article
Efficient Photosensitizer Delivery by Neutrophils for Targeted Photodynamic Therapy of Glioblastoma
by Ruojian Wen, Yuwei Liu, Xiang Tian, Yonghong Xu and Xiao Chen
Pharmaceuticals 2025, 18(2), 276; https://doi.org/10.3390/ph18020276 - 19 Feb 2025
Cited by 2 | Viewed by 766
Abstract
Background/Objectives: Glioblastoma (GBM) is the deadliest type of brain tumor and photodynamic therapy (PDT) is a promising treatment modality of GBM. However, insufficient photosensitizer distribution in the GBM critically limits the success of PDT. To address this obstacle, we propose tumoritropic neutrophils (NE) [...] Read more.
Background/Objectives: Glioblastoma (GBM) is the deadliest type of brain tumor and photodynamic therapy (PDT) is a promising treatment modality of GBM. However, insufficient photosensitizer distribution in the GBM critically limits the success of PDT. To address this obstacle, we propose tumoritropic neutrophils (NE) as active carriers for photosensitizer delivery to achieve GBM-targeted PDT. Methods: Isolated mouse NE were loaded with functionalized hexagonal boron nitride nanoparticles carrying the photosensitizer chlorin e6 (BNPD-Ce6). In vitro experiments were conducted to determine drug release from the loaded NE (BNPD-Ce6@NE) to mouse GBM cells and consequential photo-cytotoxicity. In vivo experiments were performed on mice bearing intracranial graft GBMs to demonstrate GBM-targeted drug delivery and the efficacy of anti-GBM PDT mediated by BNPD-Ce6@NE. Results: BNPD-Ce6@NE displayed good viability and migration ability, and rapidly released BNPD-Ce6 to co-cultured mouse GBM cells, which then exhibited marked reactive oxygen species (ROS) generation and cytotoxicity following 808 nm laser irradiation (LI). In the in vivo study, a single intravenous bolus injection of BNPD-Ce6@NE resulted in pronounced Ce6 distribution in intracranial graft GBMs 4 h post injection, which peaked around 8 h post injection. A PDT regimen consisting of multiple intravenous BNPD-Ce6@NE injections each followed by one extracranial tumor-directed LI 8 h post injection significantly slowed the growth of intracranial graft GBMs and markedly improved the survival of host animals. Histological analysis revealed massive tumor cell damage and NE infiltration in the PDT-treated GBMs. Conclusions: NE are efficient carriers for GBM-targeted photosensitizer delivery to achieve efficacious anti-GBM PDT. Full article
(This article belongs to the Special Issue Tumor Therapy and Drug Delivery)
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12 pages, 1579 KiB  
Article
4-Hexylresorcinol Loaded Solid Lipid Nanoparticles for Enhancing Anticancer Activity
by Sooho Yeo, Sukkyun Jung, Haneul Kim, Jun-Hyun Ahn and Sung-Joo Hwang
Pharmaceuticals 2024, 17(10), 1296; https://doi.org/10.3390/ph17101296 - 29 Sep 2024
Cited by 3 | Viewed by 1622
Abstract
Background: Cancer is one of the most significant threats to human health. Following surgical excision, chemotherapy is an effective strategy against remaining cancer cells. 4-hexylresorcinol (4-HR) has anti-cancer properties and exhibits hydrophobicity-induced aggregation in the blood that has trouble with targeted tumor delivery [...] Read more.
Background: Cancer is one of the most significant threats to human health. Following surgical excision, chemotherapy is an effective strategy against remaining cancer cells. 4-hexylresorcinol (4-HR) has anti-cancer properties and exhibits hydrophobicity-induced aggregation in the blood that has trouble with targeted tumor delivery and cellular uptake of the drug. The purpose of this study is to encapsulate 4-HR into solid lipid nanoparticles (SLNs) to enhance its anti-cancer effect by avoiding aggregation and facilitating cellular uptake. Methods: 4-HR SLNs were prepared via hot melt homogenization with sonication. SLN characteristics were assessed by analyzing particle size, zeta potential, and drug release. Cytotoxicity, as an indicator of the anti-cancer effect, was evaluated against HeLa (cervical cancer in humans), A549 (lung cancer in humans), and CT-26 (colon carcinoma in mice) cell lines. Results: Particle size ranged from 169.4 to 644.8 nm, and zeta potential ranged from −19.8 to −40.3 mV, which are conducive to cellular uptake. Entrapment efficiency (EE) of 4-HR was found to be 75.0—96.5%. The cytotoxicity of 4-HR-loaded SLNs demonstrated enhanced anti-cancer effects compared to pure 4-HR. The enhancement of anti-cancer effects depended on reduced particle size based on cellular uptake, the EE, and the cell type. Conclusions: These findings imply that 4-HR-loaded SLN is a promising strategy for chemotherapy in cancer treatment. Full article
(This article belongs to the Special Issue Tumor Therapy and Drug Delivery)
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Review

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24 pages, 1532 KiB  
Review
Polymeric Nanoparticle-Mediated Photodynamic Therapy: A Synergistic Approach for Glioblastoma Treatment
by Bandar Aldhubiab and Rashed M. Almuqbil
Pharmaceuticals 2025, 18(7), 1057; https://doi.org/10.3390/ph18071057 - 18 Jul 2025
Viewed by 463
Abstract
Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) [...] Read more.
Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) has emerged as an advanced, selective and more controlled therapeutic approach, which has minimal systemic toxicity and fewer side effects. PDT is a less invasive therapy that targets all cells or tissues that possess the photosensitizer (PS) itself, without affecting the surrounding healthy tissues. Polymeric NPs (PNPs) as carriers can improve the targeting ability and stability of PSs and co-deliver various anticancer agents to achieve combined cancer therapy. Because of their versatile tuneable features, these PNPs have the capacity to open tight junctions of the blood–brain barrier (BBB), easily transport drugs across the BBB, protect against enzymatic degradation, prolong the systemic circulation, and sustainably release the drug. Conjugated polymer NPs, poly(lactic-co-glycolic acid)-based NPs, lipid–polymer hybrid NPs, and polyethylene-glycolated PNPs have demonstrated great potential in PDT owing to their unique biocompatibility and optical properties. Although the combination of PDT and PNPs has great potential and can provide several benefits over conventional cancer therapies, there are several limitations that are hindering its translation into clinical use. This review aims to summarize the recent advances in the combined use of PNPs and PDT in the case of glioblastoma treatment. By evaluating various types of PDT and PNPs, this review emphasizes how these innovative approaches can play an important role in overcoming glioblastoma-associated critical challenges, including BBB and tumour heterogeneity. Furthermore, this review also discusses the challenges and future directions for PNPs and PDT, which provides insight into the potential solutions to various problems that are hindering their clinical translation in glioblastoma treatment. Full article
(This article belongs to the Special Issue Tumor Therapy and Drug Delivery)
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32 pages, 3717 KiB  
Review
Immunoconjugates as an Efficient Platform for Drug Delivery: A Resurgence of Natural Products in Targeted Antitumor Therapy
by Rositsa Mihaylova, Denitsa Momekova, Viktoria Elincheva and Georgi Momekov
Pharmaceuticals 2024, 17(12), 1701; https://doi.org/10.3390/ph17121701 - 17 Dec 2024
Cited by 2 | Viewed by 2304
Abstract
The present review provides a detailed and comprehensive discussion on antibody–drug conjugates (ADCs) as an evolving new modality in the current therapeutic landscape of malignant diseases. The principle concepts of targeted delivery of highly toxic agents forsaken as stand-alone drugs are examined in [...] Read more.
The present review provides a detailed and comprehensive discussion on antibody–drug conjugates (ADCs) as an evolving new modality in the current therapeutic landscape of malignant diseases. The principle concepts of targeted delivery of highly toxic agents forsaken as stand-alone drugs are examined in detail, along with the biochemical and technological tools for their successful implementation. An extensive analysis of ADCs’ major components is conducted in parallel with their function and impact on the stability, efficacy, safety, and resistance profiles of the immunoconjugates. The scope of the article covers the major classes of currently validated natural compounds used as payloads, with an emphasis on their structural and mechanistic features, natural origin, and distribution. Future perspectives in ADCs’ design are thoroughly explored, addressing their inherent or emerging challenges and limitations. The survey also provides a comprehensive overview of the molecular rationale for active tumor targeting of ADC-based platforms, exploring the cellular biology and clinical relevance of validated tumor markers used as a “homing” mechanism in both hematological and solid tumor malignancies. Full article
(This article belongs to the Special Issue Tumor Therapy and Drug Delivery)
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23 pages, 2007 KiB  
Review
Targeting Tumor Hypoxia with Nanoparticle-Based Therapies: Challenges, Opportunities, and Clinical Implications
by Sujit Kumar Debnath, Monalisha Debnath, Arnab Ghosh, Rohit Srivastava and Abdelwahab Omri
Pharmaceuticals 2024, 17(10), 1389; https://doi.org/10.3390/ph17101389 - 18 Oct 2024
Cited by 10 | Viewed by 3604
Abstract
Hypoxia is a crucial factor in tumor biology, affecting various solid tumors to different extents. Its influence spans both early and advanced stages of cancer, altering cellular functions and promoting resistance to therapy. Hypoxia reduces the effectiveness of radiotherapy, chemotherapy, and immunotherapy, making [...] Read more.
Hypoxia is a crucial factor in tumor biology, affecting various solid tumors to different extents. Its influence spans both early and advanced stages of cancer, altering cellular functions and promoting resistance to therapy. Hypoxia reduces the effectiveness of radiotherapy, chemotherapy, and immunotherapy, making it a target for improving therapeutic outcomes. Despite extensive research, gaps persist, necessitating the exploration of new chemical and pharmacological interventions to modulate hypoxia-related pathways. This review discusses the complex pathways involved in hypoxia and the associated pharmacotherapies, highlighting the limitations of current treatments. It emphasizes the potential of nanoparticle-based platforms for delivering anti-hypoxic agents, particularly oxygen (O2), to the tumor microenvironment. Combining anti-hypoxic drugs with conventional cancer therapies shows promise in enhancing remission rates. The intricate relationship between hypoxia and tumor progression necessitates novel therapeutic strategies. Nanoparticle-based delivery systems can significantly improve cancer treatment efficacy by targeting hypoxia-associated pathways. The synergistic effects of combined therapies underscore the importance of multimodal approaches in overcoming hypoxia-mediated resistance. Continued research and innovation in this area hold great potential for advancing cancer therapy and improving patient outcomes. Full article
(This article belongs to the Special Issue Tumor Therapy and Drug Delivery)
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