Abstract
Although being a heterogeneous disease, cancer has certain characteristic features which can be utilized for treatment with novel macromolecular therapeutics. The active cycling status of tumor cells, proliferating tumor endothelium and a leaky vasculature allow the targeted delivery of therapeutically active nucleic acids into tumor tissue. We and others have developed polycationic gene carriers forming so called polyplexes with nucleic acids. Cellular aspects like binding, internalization and intracellular fate were enlightened. Additionally, virus like domains were incorporated into the polyplex. Hydrophilic shielding domains protect the polyplex from unspecific interaction with blood components, targeting ligands allow cell specific binding and internalization into target cells, and membrane active peptides have a favorable influence on intracellular trafficking. Physical targeting of polyplexes, like locoregional hyperthermia and photochemical internalization (PCI) have been further used to enhance the efficiency of nucleic acid transfer. Therapeutic concepts were carried out in different tumor models in mice. Local application of synthetic, double stranded RNA led to eradication of intracranial glioblastoma. A gene directed enzyme prodrug approach utilizing site directed activation of cyclophosphamide with cytochrome P450 gave first, promising results.
Keywords: Nonviral gene delivery, gene therapy, tumor targeting
Anti-Cancer Agents in Medicinal Chemistry
Title: Nucleic Acid Based Therapeutics for Tumor Therapy
Volume: 6 Issue: 6
Author(s): Manfred Ogris
Affiliation:
Keywords: Nonviral gene delivery, gene therapy, tumor targeting
Abstract: Although being a heterogeneous disease, cancer has certain characteristic features which can be utilized for treatment with novel macromolecular therapeutics. The active cycling status of tumor cells, proliferating tumor endothelium and a leaky vasculature allow the targeted delivery of therapeutically active nucleic acids into tumor tissue. We and others have developed polycationic gene carriers forming so called polyplexes with nucleic acids. Cellular aspects like binding, internalization and intracellular fate were enlightened. Additionally, virus like domains were incorporated into the polyplex. Hydrophilic shielding domains protect the polyplex from unspecific interaction with blood components, targeting ligands allow cell specific binding and internalization into target cells, and membrane active peptides have a favorable influence on intracellular trafficking. Physical targeting of polyplexes, like locoregional hyperthermia and photochemical internalization (PCI) have been further used to enhance the efficiency of nucleic acid transfer. Therapeutic concepts were carried out in different tumor models in mice. Local application of synthetic, double stranded RNA led to eradication of intracranial glioblastoma. A gene directed enzyme prodrug approach utilizing site directed activation of cyclophosphamide with cytochrome P450 gave first, promising results.
Export Options
About this article
Cite this article as:
Ogris Manfred, Nucleic Acid Based Therapeutics for Tumor Therapy, Anti-Cancer Agents in Medicinal Chemistry 2006; 6 (6) . https://dx.doi.org/10.2174/187152006778699158
DOI https://dx.doi.org/10.2174/187152006778699158 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Targeting mTOR: Evaluating the Therapeutic Potential of Resveratrol for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Synthetic Methods of Quinoline Derivatives as Potent Anticancer Agents
Mini-Reviews in Medicinal Chemistry Computational Studies on the Prion Protein
Current Topics in Medicinal Chemistry Molecular and Biological Heterogeneity in Neuroblastoma
Current Genomics Building Better Chimeric Antigen Receptors for Adoptive T Cell Therapy
Current Gene Therapy Papillary Thyroid Carcinoma in Pediatric Age: An Example of a Rare Tumour Managed Within a Cooperative Comprehensive Project
Current Pediatric Reviews A Combination of Two Antioxidants (An SOD Mimic and Ascorbate) Produces a Pro-Oxidative Effect Forcing Escherichia coli to Adapt Via Induction of oxyR Regulon
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in the Molecular Pathogenesis of Dystonia-Plus Syndromes and Heredodegenerative Dystonias
Current Neuropharmacology Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions
Current Drug Targets Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Current Pharmaceutical Design Glial Cells – The Key Elements of Alzheimer´s Disease
Current Alzheimer Research A Review on Anti-Cancer Activity of Some of the Oil-Soluble Organosulphur Compounds Against Colon Cancer
Current Traditional Medicine Curcumin, Resveratrol and Cannabidiol as Natural Key Prototypes in Drug Design for Neuroprotective Agents
Current Neuropharmacology Natural Antioxidants: Therapeutic Prospects for Cancer and Neurological Diseases
Mini-Reviews in Medicinal Chemistry Tumor Angiogenesis: A Potential Target In Cancer Control by Phytochemicals
Current Cancer Drug Targets Involvement of Trace Elements in the Pathogenesis of Prion Diseases
Current Pharmaceutical Biotechnology Regulators of Chemokine Receptor Activity as Promising Anticancer Therapeutics
Current Cancer Drug Targets Dietary Phytoestrogens: Neuroprotective Role in Parkinson’s Disease
Current Neurovascular Research Decreasing the Metastatic Potential in Cancers - Targeting the Heparan Sulfate Proteoglycans
Current Drug Targets Getting Rid of Intracellular Aβ - Loss of Cellular Degradation Leads to Transfer Between Connected Neurons
Current Pharmaceutical Design