Abstract
Photodynamic therapy (PDT), the concept of cancer treatment through the selective uptake of a light-sensitive agent followed by exposure to a specific wavelength, is limited by the transport of a photosensitizer (PS) to the tumor tissue. Porphyrin, an important PS class, can be used in PDT in the form of its prodrug molecule 5-aminolevulinic acid (5-ALA). Unfortunately, its poor pharmacokinetic properties make this compound difficult to administer. Two different methods for eliminating this problem can be distinguished. The first approach is to play with its formulation in order to improve the drugs applicability. The second approach, which is to find possible 5- ALA prodrugs, is an example of the double-prodrug method, a strategy often used in modern drug design. In this approach, the biological mechanisms in a long biosynthetic pathway involving several steps must be completed before the active drug appears. Recently, an idea of enhancing PDT sensitization using the so-called iron chelators seemed to increase the accumulation of protoporphyrin in cells. At the same time, iron chelators can destroy tumor cells by producing active oxygen after the formation of an active drug by chelating iron in the cancer cells. Thus, in the latter case, the therapy resembles a prodrug strategy. The mechanism can be explained by the Fenton reaction. Vitamin C is another example of a potential anticancer agent of this type.
Keywords: Prodrug, photodynamic therapy, iron chelators, aminolevulinic acid, anticancer agent, lipophilicity, pharmacokinetics, chemotherapeutics, oxidative stress, hydrogen peroxide
Current Pharmaceutical Design
Title: Prodrugs in Photodynamic Anticancer Therapy
Volume: 17 Issue: 32
Author(s): Robert Musiol, Maciej Serda and Jaroslaw Polanski
Affiliation:
Keywords: Prodrug, photodynamic therapy, iron chelators, aminolevulinic acid, anticancer agent, lipophilicity, pharmacokinetics, chemotherapeutics, oxidative stress, hydrogen peroxide
Abstract: Photodynamic therapy (PDT), the concept of cancer treatment through the selective uptake of a light-sensitive agent followed by exposure to a specific wavelength, is limited by the transport of a photosensitizer (PS) to the tumor tissue. Porphyrin, an important PS class, can be used in PDT in the form of its prodrug molecule 5-aminolevulinic acid (5-ALA). Unfortunately, its poor pharmacokinetic properties make this compound difficult to administer. Two different methods for eliminating this problem can be distinguished. The first approach is to play with its formulation in order to improve the drugs applicability. The second approach, which is to find possible 5- ALA prodrugs, is an example of the double-prodrug method, a strategy often used in modern drug design. In this approach, the biological mechanisms in a long biosynthetic pathway involving several steps must be completed before the active drug appears. Recently, an idea of enhancing PDT sensitization using the so-called iron chelators seemed to increase the accumulation of protoporphyrin in cells. At the same time, iron chelators can destroy tumor cells by producing active oxygen after the formation of an active drug by chelating iron in the cancer cells. Thus, in the latter case, the therapy resembles a prodrug strategy. The mechanism can be explained by the Fenton reaction. Vitamin C is another example of a potential anticancer agent of this type.
Export Options
About this article
Cite this article as:
Musiol Robert, Serda Maciej and Polanski Jaroslaw, Prodrugs in Photodynamic Anticancer Therapy, Current Pharmaceutical Design 2011; 17 (32) . https://dx.doi.org/10.2174/138161211798194549
DOI https://dx.doi.org/10.2174/138161211798194549 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pharmacological Potential of Exercise and RAS Vasoactive Peptides for Prevention of Diseases
Current Protein & Peptide Science The Role of Venous Abnormalities in Neurological Disease
Reviews on Recent Clinical Trials Computational Studies of Competitive Inhibitors of Nitric Oxide Synthase (NOS) Enzymes: Towards the Development of Powerful and Isoform-Selective Inhibitors
Current Medicinal Chemistry Natural and Semi synthetic Antimalarial Compounds: Emphasis on the Terpene Class
Mini-Reviews in Medicinal Chemistry Maternal Outcomes in Women with Major Degree Placenta Previa: An Observational Cohort Study
Current Women`s Health Reviews The Role of Growth Factors in the Prevention and Treatment of Chemotherapy-Induced Peripheral Neurotoxicity
Current Drug Safety Blood Pressure as a Therapeutic Target in Stroke
Current Topics in Medicinal Chemistry Small Interfering RNAs and Antisense Oligonucleotides for Treatment of Neurological Diseases
Current Drug Targets The Impact of Natural Compounds on the Treatment of Neurodegenerative Diseases
Current Organic Chemistry Pulmonary Vasodilators in the Management of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery
Current Vascular Pharmacology Structural and Pharmacological Features of Phospholipases A2 from Snake Venoms
Protein & Peptide Letters Adverse Drug Reactions Amongst Adult Patients Admitted in Lagos State University Teaching Hospital Lagos, Nigeria
Current Drug Safety Markers of Individual Drug Metabolism: Towards the Development of a Personalized Antidepressant Prescription
Current Drug Metabolism Beta-Blockers in Pediatric Hypertrophic Cardiomyopathies
Reviews on Recent Clinical Trials Genetics of Polygenic Hypertension from Animal Models to Humans
Current Hypertension Reviews The Cancer Related Thrombotic Tendency in Sepsis
Current Drug Targets Gender Differences in Response to Therapy for Cardiovascular Diseases
Current Pharmacogenomics and Personalized Medicine Role of Chronotherapy in the Management of Hypertension: An Overview
Current Drug Therapy Life Threatening and Fatal Contrast Media Reactions: Pathomechanisms, Diagnosis, Prevention and Drug Management
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Current Strategies to Achieve Further Cardiac and Renal Protection through Enhanced Renin-Angiotensin-Aldosterone System Inhibition
Reviews on Recent Clinical Trials