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Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward...
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Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 7504

Special Issue Editors

Dr. Andreas Tzakos

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Guest Editor
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
Interests: drug development; theranostics; diagnostics; therapeutics; plant extracts
Special Issues, Collections and Topics in MDPI journals
Dr. Tim R. Crook

E-Mail Website
Guest Editor
Department of Oncology, The London Clinic, London W1G 6BW, UK
Interests: bladder cancer; breast cancer; melanoma; renal; skin cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Nelofer Syed

E-Mail Website
Guest Editor
Department of Brain Sciences, Imperial College London, London SW7 2AZ, UK
Interests: oncology and carcinogenesis; neurosciences; clinical sciences; biochemistry and cell biology; pharmacology and pharmaceutical sciences
Dr. George Alexiou

E-Mail Website
Guest Editor
Department of Neurosurgery, University of Ioannina, GR 451 10 Ioannina, Greece
Interests: theranostic; plant derived agents; flow cytometry; neurosurgery; oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue invites contributions addressing innovative strategies in the diagnosis, treatment, and personalized management of cancer. It highlights advancements in drug delivery systems, theranostics, diagnostics, and the tumor microenvironment while emphasizing personalized oncology approaches to enhance therapeutic outcomes. Submissions may include original research, comprehensive reviews, or case studies in the following areas:

  • Drug Delivery Innovations:
    • Design and development of personalized, targeted drug delivery systems for cancer.
    • Novel nanoparticle-based, lipid-based, or polymeric carriers tailored to patient-specific tumor profiles.
    • Overcoming biological barriers to achieve selective delivery to metastatic sites.
  • Therapeutics:
    • Development of personalized therapies, including small molecules, biologics, and immunotherapies.
    • Advances in radiation-based therapies integrated with personalized treatment strategies.
    • Exploration of combination therapies targeting patient-specific metastatic pathways.
  • Theranostics:
    • Design of multifunctional agents that combine diagnostic and therapeutic capabilities for personalized oncology.
    • Innovations in fluorescence-based or radiolabeled probes tailored to individual tumor biology.
    • Real-time monitoring tools for treatment response and cancer tracking.
  • Diagnostics and Biomarkers:
    • Discovery of novel biomarkers for the early detection and progression monitoring of metastatic cancers.
    • Development of personalized fluorescent sensors for the dynamic assessment of tumor microenvironment conditions.
    • Multi-omics approaches for the identification of patient-specific predictive biomarkers and treatment customization.
  • Emerging Technologies:
    • Application of cutting-edge technologies in tailoring therapeutic and diagnostic approaches for cancer.
    • Novel platforms for integrating personalized medicine into oncology practice.

Dr. Andreas Tzakos
Dr. Tim R. Crook
Dr. Nelofer Syed
Dr. George Alexiou
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 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

  • personalized medicine
  • cancer diagnostics
  • cancer therapeutics
  • cancer theranostics
  • radiotherapeutics
  • precision oncology
  • targeted therapy
  • immunotherapy
  • molecular diagnostics
  • biomarkers in cancer
  • cancer genomics
  • tumor microenvironment
  • surgical oncology
  • cancer biomarkers
  • AI in cancer diagnosis
  • multimodal cancer treatment
  • advanced imaging in oncology

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

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Research

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21 pages, 2546 KB  
Article
Mesoscopic Fluorescence Imaging of Light-Triggered Chemotherapeutic Release in Cancer Spheroid Models
by Elias Kluiszo, Rasel Ahmmed, Berna Aliu, Semra Aygun-Sunar, Matthew Willadsen, Hilliard L. Kutscher, Jonathan F. Lovell and Ulas Sunar
Pharmaceutics 2026, 18(4), 495; https://doi.org/10.3390/pharmaceutics18040495 - 17 Apr 2026
Viewed by 211
Abstract
Background/Objectives: Peritoneal micrometastases (micromets) remain a major barrier to durable cytoreduction in ovarian and other intra-abdominal cancers because lesions are difficult to visualize and are often resistant to systemic therapy. Liposomal doxorubicin (Dox) improves pharmacokinetics but can be limited by slow intratumoral release. [...] Read more.
Background/Objectives: Peritoneal micrometastases (micromets) remain a major barrier to durable cytoreduction in ovarian and other intra-abdominal cancers because lesions are difficult to visualize and are often resistant to systemic therapy. Liposomal doxorubicin (Dox) improves pharmacokinetics but can be limited by slow intratumoral release. Porphyrin-phospholipid (PoP) liposomes enable near-infrared light–triggered release of Dox (chemophototherapy (CPT)), creating an opportunity for intraoperative fluorescence-guided treatment planning and monitoring. Here, we evaluate a laparoscopic fluorescence imaging platform for quantifying light-triggered drug delivery. Methods: LC-Dox-PoP was applied to SCC2095sc and SKOV-3 cultures in 2D monolayers and 3D spheroid clusters. Dox fluorescence was quantified using a laparoscopic fluorescence imaging system over 1–9 μg/mL concentrations and compared with standard well-plate reader measurements. Porphyrin fluorescence was monitored to assess spheroid localization and photobleaching after activation light exposure. Results: For both cell lines, Dox fluorescence exhibited an approximate 4-fold increase at the maximum administered LC-Dox-PoP concentration, following a linear trend in both SCC2095sc and SKOV-3 cultures (R2 = 0.97, 0.98 for 2D and R2 = 0.98, 0.98 for spheroids). Laparoscope-derived fluorescence measurements agreed with well-plate reader measurements (R2 = 0.89–0.96). Porphyrin fluorescence provided stronger complementary contrast for localizing spheroid constructs and decreased after activation light exposure, consistent with photobleaching during triggered release. Conclusions: These results support a quantitative imaging framework for fluorescence-guided monitoring of light-triggered liposomal drug release and may enable individualized CPT dosimetry for peritoneal micrometastases. Findings in SCC2095sc additionally suggest potential relevance of fluorescence-guided CPT for head and neck/oral cancer, where localized post-resection adjuvant treatment may improve control of residual disease. Full article
(This article belongs to the Special Issue Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology)
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18 pages, 3759 KB  
Article
Effects of Proglumide with Chemotherapy on the Pancreatic Tumor Microenvironment: Phase 1 PROGEM Trial
by Jill P. Smith, Gakiza C. Nkulikiyimana, Hong Cao, Wenqiang Chen, Bhaskar Kallakury, John Kwagyan, Anju Duttargi and Benjamin A. Weinberg
Pharmaceutics 2026, 18(3), 379; https://doi.org/10.3390/pharmaceutics18030379 - 19 Mar 2026
Viewed by 689
Abstract
Background: The primary aim of this Phase 1 clinical trial was to study the safety and dose of a cholecystokinin receptor antagonist, proglumide, in combination with gemcitabine/nab-paclitaxel (GEM-NAB-P) in patients with metastatic pancreatic cancer. The secondary aim was to study the effects [...] Read more.
Background: The primary aim of this Phase 1 clinical trial was to study the safety and dose of a cholecystokinin receptor antagonist, proglumide, in combination with gemcitabine/nab-paclitaxel (GEM-NAB-P) in patients with metastatic pancreatic cancer. The secondary aim was to study the effects of proglumide with GEM-NAB-P on the tumor microenvironment (TME) with tumor biopsies and a blood biomarker assay. An exploratory aim studied the effects of proglumide treatment on cancer-related pain. Methods: Gemcitabine-naïve patients were treated with GEM-NAB-P plus proglumide 1200 mg/day. Tumor biopsies and a liquid biopsy serum sample for analysis of a microRNA biomarker panel were collected pre- and on-treatment to study the TME. McGill pain surveys were done at baseline, week 8 and at the end of treatment. The study was approved and registered (NCT05827055). Results: The mean age of the patients was 68.2 years (range 54–74 years). The starting dose was well-tolerated with no unexpected treatment-related adverse events observed. Multiplex immunohistochemical analysis of tumor biopsies at baseline and week 8 revealed a significant reduction in Ki67+ cells, collagen1α1, and M2-polarized tumor-associated macrophages (TAMs). Week 8 tumor biopsies demonstrated a significant increase in CD8+ T-cells and natural killer cells compared to baseline. The blood biomarker panel showed a significant inverse change in microRNAs associated with decreasing fibrosis and metastasis. The McGill pain scores showed less pain at week 24 or end-of-treatment compared to baseline. Conclusions: Proglumide demonstrates a favorable safety profile when combined with standard chemotherapy for metastatic pancreatic cancer. Its unique ability to remodel TME and alleviate cancer-related pain highlights its potential, warranting further research. Full article
(This article belongs to the Special Issue Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology)
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20 pages, 5919 KB  
Article
Optimization of Intraoperative Near-Infrared Fluorescence Mapping with Indocyanine Green for Sentinel Lymph Node Detection in Cervical and Endometrial Cancer
by Kanamat Efendiev, Maria Meshkova, Polina Alekseeva, Andrei Udeneev, Arkadii Moskalev, Maxim Loshchenov, Heda Maltsagova, Svetlana Mukhtarulina, Andrey Kaprin and Victor Loschenov
Pharmaceutics 2026, 18(2), 211; https://doi.org/10.3390/pharmaceutics18020211 - 6 Feb 2026
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Abstract
Background/Objectives: Lymph node dissection during surgeries for cervical and endometrial cancer is associated with significant complications and morbidity. Sentinel lymph nodes (SLNs) mapping using indocyanine green (ICG) has become a promising method for reducing surgical invasiveness and improving patient outcomes. However, the optimal [...] Read more.
Background/Objectives: Lymph node dissection during surgeries for cervical and endometrial cancer is associated with significant complications and morbidity. Sentinel lymph nodes (SLNs) mapping using indocyanine green (ICG) has become a promising method for reducing surgical invasiveness and improving patient outcomes. However, the optimal protocol for intraoperative fluorescence mapping of SLNs using ICG, especially regarding the timing of imaging after injection, remains to be fully optimized. This study aimed to evaluate the efficacy of real-time near-infrared (NIR) fluorescence SLN mapping at various time intervals and to investigate the photophysical properties of ICG in human lymph to establish a correlation between fluorescence signals and dye concentration. Methods: A prospective study included 20 patients with cervical and endometrial cancer undergoing laparoscopic or laparotomic surgery. Interstitial ICG injection was administered into the cervical stroma. SLN mapping was conducted using the novel VENERA-green endoscopic system (λexc = 800 nm, registration of fluorescence in the range of 830–1000 nm). Spectral fluorescence analysis (λexc = 650 nm) was conducted on SLNs and optical phantoms containing human lymph with ICG concentrations from 0 to 40 mg/L. The method made it possible to evaluate ICG absorption/emission properties, as well as to quantify concentration-dependent effects. Results: SLNs were successfully detected in all patients. The average detection time was 15 min with a range of 10 to 25 min. Fluorescence intensity of SLNs was significantly higher 10–15 min after ICG injection compared to 20–25 min. Spectral analysis indicated an absorption peak at 804 nm and an emission peak in the 835–855 nm range for ICG in human lymph. A concentration-dependent redshift of the fluorescence peak was observed and accurately modeled using a logarithmic function (R2 = 0.99), which allows for the estimation of ICG concentration in tissue. The bilateral detection rate was 77% for laparoscopy and 100% for laparotomy. Metastases were histologically confirmed in only 2.8% (1/36) of the detected SLNs. Conclusions: Intraoperative NIR fluorescence imaging using ICG is a highly sensitive method for real-time SLN mapping in gynecologic oncology. The optimal detection period is 10 to 15 min after cervical injection to achieve maximum ICG fluorescence intensity, compared to 20 to 25 min. The concentration-dependent fluorescence and absorption properties of ICG in lymph provide the basis for the development of quantitative intraoperative monitoring methods that could improve the accuracy of sentinel lymph node biopsy. Full article
(This article belongs to the Special Issue Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology)
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Review

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50 pages, 4888 KB  
Review
Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies
by Bárbara Pinto, João P. N. Silva, Patrícia M. A. Silva, Bruno Sarmento, Juliana Carvalho-Tavares and Hassan Bousbaa
Pharmaceutics 2026, 18(4), 402; https://doi.org/10.3390/pharmaceutics18040402 - 24 Mar 2026
Viewed by 755
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide and is characterized by high aggressiveness and therapeutic resistance, partly driven by mitotic dysregulation. Key mitotic regulators, including kinases such as PLK1, AURKA, AURKB, and MPS1 and kinesins such as CENPE and Eg5, [...] Read more.
Lung cancer remains the leading cause of cancer-related mortality worldwide and is characterized by high aggressiveness and therapeutic resistance, partly driven by mitotic dysregulation. Key mitotic regulators, including kinases such as PLK1, AURKA, AURKB, and MPS1 and kinesins such as CENPE and Eg5, are frequently overexpressed in NSCLC and SCLC, contributing to chromosomal instability, aneuploidy, and highly proliferative tumor phenotypes. Although multiple inhibitors targeting these proteins have been developed, their clinical efficacy as monotherapies has been limited. This is largely due to insufficient target dependency, adaptive resistance mechanisms, mitotic slippage, activation of compensatory pathways, and dose-limiting toxicity. This review integrates current knowledge on the physiological roles of major mitotic regulators, their dysregulation in lung tumorigenesis, and the biological and pharmacological barriers that underlie the limited success of antimitotic drugs. We further highlight preclinical and clinical evidence supporting rational combination strategies designed to enhance the antitumor activity of mitotic inhibitors while minimizing toxicity. Together, these insights underscore the need for refined therapeutic approaches that better exploit vulnerabilities in mitotic control to improve outcomes for patients with lung cancer. Full article
(This article belongs to the Special Issue Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology)
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13 pages, 542 KB  
Review
Pharmacogenomics of Antineoplastic Therapy in Children: Genetic Determinants of Toxicity and Efficacy
by Zaure Dushimova, Timur Saliev, Aigul Bazarbayeva, Gaukhar Nurzhanova, Ainura Baibadilova, Gulnara Abdilova and Ildar Fakhradiyev
Pharmaceutics 2026, 18(2), 165; https://doi.org/10.3390/pharmaceutics18020165 - 27 Jan 2026
Viewed by 739
Abstract
Over the past decades, remarkable progress in multimodal therapy has significantly improved survival outcomes for children with cancer. Yet, considerable variability in treatment response and toxicity persists, often driven by underlying genetic differences that affect the pharmacokinetics and pharmacodynamics of anticancer drugs. Pharmacogenomics, [...] Read more.
Over the past decades, remarkable progress in multimodal therapy has significantly improved survival outcomes for children with cancer. Yet, considerable variability in treatment response and toxicity persists, often driven by underlying genetic differences that affect the pharmacokinetics and pharmacodynamics of anticancer drugs. Pharmacogenomics, the study of genetic determinants of drug response, offers a powerful approach to personalize pediatric cancer therapy by optimizing efficacy while minimizing adverse effects. This review synthesizes current evidence on key pharmacogenetic variants influencing the response to major classes of antineoplastic agents used in children, including thiopurines, methotrexate, anthracyclines, alkylating agents, vinca alkaloids, and platinum compounds. Established gene–drug associations such as TPMT, NUDT15, DPYD, SLC28A3, and RARG are discussed alongside emerging biomarkers identified through genome-wide and multi-omics studies. The review also examines the major challenges that impede clinical implementation, including infrastructural limitations, cost constraints, population-specific variability, and ethical considerations. Furthermore, it highlights how integrative multi-omics, systems pharmacology, and artificial intelligence may accelerate the translation of pharmacogenomic data into clinical decision-making. The integration of pharmacogenomic testing into pediatric oncology protocols has the potential to transform cancer care by improving drug safety, enhancing treatment precision, and paving the way toward ethically grounded, personalized therapy for children. Full article
(This article belongs to the Special Issue Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology)
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22 pages, 1049 KB  
Review
Agents for Fluorescence-Guided Glioblastoma Surgery
by Eleni Romeo, Andreas G. Tzakos, Timothy Crook, Nelofer Syed, Spyridon Voulgaris and George A. Alexiou
Pharmaceutics 2025, 17(5), 637; https://doi.org/10.3390/pharmaceutics17050637 - 11 May 2025
Cited by 3 | Viewed by 3236
Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression and a median survival of no more than 12–18 months. Fluorescence-guided surgery is crucial, as it allows for tumor visualization and aids in its complete removal, which is essential for [...] Read more.
Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression and a median survival of no more than 12–18 months. Fluorescence-guided surgery is crucial, as it allows for tumor visualization and aids in its complete removal, which is essential for improving survival rates. We conducted a literature review to identify fluorescent agents that have been utilized in the removal of GBM and to assess their benefits in achieving maximum tumor resection. Our analysis focuses on their advantages, limitations, and potential impact on improving surgical precision and patient outcomes. We searched the PubMed database for studies published on fluorescence-guided resection of GBM and evaluated the utility of each agent in terms of outcomes, gross total resection (GTR), and their sensitivity and specificity for the tumor. The literature review revealed that the three agents successfully utilized are 5-aminolevulinic acid (5-ALA), sodium fluorescein, and indocyanine green. In addition to these, a variety of dyes have been investigated in studies, including peptides, lipids, and nanosystems, which appear to be very promising. To date, numerous fluorescent agents have been proposed for the surgical resection of GBM. However, 5-aminolevulinic acid (5-ALA) remains the only agent widely adopted in clinical practice, as its safety and efficacy have been well-established. Further clinical trials and studies are necessary to assess the utility, effectiveness, and potential advantages of emerging fluorescent dyes in enhancing GBM resection and improving patient outcomes. Full article
(This article belongs to the Special Issue Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology)
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