Abstract
Platinum-based anticancer chemotherapy is associated to severe side effects because of its poor specificity. In particular, the hydrolysis of Pt-based drugs generates cationic complexes with electrophylic properties able to target DNA. The effectiveness of this kind of chemotherapy relies solely on the proliferation index of tumour cells, which is higher than in healthy cells. In recent years, the “drug targeting and delivery” approach has been developed in an attempt to reduce chemotherapy-related systemic side effects by using vectors that selectively deliver the cytotoxic agent to tumour cells, thus sparing healthy cells. These vectors include bioactive substances, such as nutrients, that more readily enter metabolically active tumour cells, or hormones, folates and bile acids, that are selectively conveyed by receptors/transporters often over-expressed in cancer cells (active targeting). Alternatively, macromolecular vectors, exploiting the so-called EPR (enhanced permeability and retention) effect, can be used (passive targeting). The bioactive or macromolecular vector must contain a coordinating arm capable of binding the PtX2-unit, acting either as carrier or leaving group for the cytotoxic Pt-moiety. In both cases, the Pt-vector conjugate should be promptly cleaved to generate the active species. The release of platinum drugs from the pharmacophore is crucial for fine-tuning of the overall cytotoxic properties of the conjugates. The “drug targeting and delivery” method represents an exciting field of research for improving the therapeutic potential of the long established, very efficient, but intrinsically non-specific Pt-based drugs.
Keywords: Anticancer Pt-based drugs, drug targeting and delivery, EPR effect
Current Medicinal Chemistry
Title: The Drug Targeting and Delivery Approach Applied to Pt-Antitumour Complexes. A Coordination Point of View
Volume: 16 Issue: 34
Author(s): E. Gabano, M. Ravera and D. Osella
Affiliation:
Keywords: Anticancer Pt-based drugs, drug targeting and delivery, EPR effect
Abstract: Platinum-based anticancer chemotherapy is associated to severe side effects because of its poor specificity. In particular, the hydrolysis of Pt-based drugs generates cationic complexes with electrophylic properties able to target DNA. The effectiveness of this kind of chemotherapy relies solely on the proliferation index of tumour cells, which is higher than in healthy cells. In recent years, the “drug targeting and delivery” approach has been developed in an attempt to reduce chemotherapy-related systemic side effects by using vectors that selectively deliver the cytotoxic agent to tumour cells, thus sparing healthy cells. These vectors include bioactive substances, such as nutrients, that more readily enter metabolically active tumour cells, or hormones, folates and bile acids, that are selectively conveyed by receptors/transporters often over-expressed in cancer cells (active targeting). Alternatively, macromolecular vectors, exploiting the so-called EPR (enhanced permeability and retention) effect, can be used (passive targeting). The bioactive or macromolecular vector must contain a coordinating arm capable of binding the PtX2-unit, acting either as carrier or leaving group for the cytotoxic Pt-moiety. In both cases, the Pt-vector conjugate should be promptly cleaved to generate the active species. The release of platinum drugs from the pharmacophore is crucial for fine-tuning of the overall cytotoxic properties of the conjugates. The “drug targeting and delivery” method represents an exciting field of research for improving the therapeutic potential of the long established, very efficient, but intrinsically non-specific Pt-based drugs.
Export Options
About this article
Cite this article as:
Gabano E., Ravera M. and Osella D., The Drug Targeting and Delivery Approach Applied to Pt-Antitumour Complexes. A Coordination Point of View, Current Medicinal Chemistry 2009; 16 (34) . https://dx.doi.org/10.2174/092986709789760661
DOI https://dx.doi.org/10.2174/092986709789760661 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- 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
-
Development and Engineering of Lymphatic Endothelial Cells: Clinical Implications
Current Pharmaceutical Design The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention
Anti-Cancer Agents in Medicinal Chemistry Novel Beta-Lactam Antibiotics Derivatives: Their New Applications as Gene Reporters, Antitumor Prodrugs and Enzyme Inhibitors
Mini-Reviews in Medicinal Chemistry Characteristic Alterations of Nuclear Structure and Chromatin Organisation of Cancer Cells Addressed by Proteome Analysis**
Current Proteomics Revising Skin Cancers by Means of Epigenetic Markers
Recent Patents on Biomarkers Bortezomib as the First Proteasome Inhibitor Anticancer Drug: Current Status and Future Perspectives
Current Cancer Drug Targets Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies
Anti-Cancer Agents in Medicinal Chemistry S-Phase Kinase-Associated Protein-2 and Nuclear Factor-kappa Beta as Molecular Targets of Oral Burkitt’s Lymphoma Cell Induced by Quinolinone Derivate-Vesnarinone
Current Signal Transduction Therapy Cancer Stem Cell Markers in Nasopharyngeal Carcinoma and Its Relevance for Therapy
Current Traditional Medicine Trends in the Exploration of Anticancer Targets and Strategies in Enhancing the Efficacy of Drug Targeting
Current Molecular Pharmacology Optimizing Gene Silencing Strategies for Pancreatic Cancer
Current Cancer Therapy Reviews Opportunities to Improve the Prevention and Treatment of Cervical Cancer
Current Molecular Medicine Anti-Cancer Potential of Some Commonly Used Drugs
Current Pharmaceutical Design Recent Patents on Biomedical Devices and Nanomaterials for Hyperthermal Therapy of Cancer
Recent Patents on Nanomedicine Pancreatic Cancer and Personalized Medicine: Can Genomics Facilitate Early Diagnosis or Improve Therapeutic Outcomes?
Current Pharmacogenomics and Personalized Medicine The Role of Integrins in Glioma Biology and Anti-Glioma Therapies
Current Pharmaceutical Design Merkel Cell Carcinoma – Current State and the Future
Current Cancer Therapy Reviews Clinical Impact of Gene Expression Profiling on Oncology Diagnosis, Prognosis, and Treatment
Combinatorial Chemistry & High Throughput Screening Drug Delivery to the Inner Ear: Strategies and Their Therapeutic Implications for Sensorineural Hearing Loss
Current Drug Delivery Medical Treatment of Malignancy-Associated Hypercalcemia
Current Medicinal Chemistry