Abstract
Bone metastases contribute to morbidity in patients with common cancers, and conventional therapy provides only palliation and can induce systemic side effects. The development of nanostructured delivery systems that combine carriers with bone-targeting molecules can potentially overcome the drawbacks presented by conventional approaches. We have recently developed biodegradable, biocompatible nanoparticles (NP) made of a conjugate between poly (D,Llactide- co-glycolic) acid and alendronate, suitable for systemic administration, and directly targeting the site of tumorinduced osteolysis. Here, we loaded NP with doxorubicin (DXR), and analyzed the in vitro and in vivo activity of the drug encapsulated in the carrier system. After confirming the intracellular uptake of DXR-loaded NP, we evaluated the antitumor effects in a panel of human cell lines, representative for primary or metastatic bone tumors, and in an orthotopic mouse model of breast cancer bone metastases. In vitro, both free DXR and DXR-loaded NP, (58-580 ng/mL) determined a significant dose-dependent growth inhibition of all cell lines. Similarly, both DXR-loaded NP and free DXR reduced the incidence of metastases in mice. Unloaded NP were ineffective, although both DXR-loaded and unloaded NP significantly reduced the osteoclast number at the tumor site (P = 0.014, P = 0.040, respectively), possibly as a consequence of alendronate activity. In summary, NP may act effectively as a delivery system of anticancer drugs to the bone, and deserve further evaluation for the treatment of bone tumors.
Keywords: Bisphosphonates, bone targeting, doxorubicin, drug delivery system, nanoparticles, osteolysis, skeletal metastases.
Current Cancer Drug Targets
Title:Bone-Targeted Doxorubicin-Loaded Nanoparticles as a Tool for the Treatment of Skeletal Metastases
Volume: 10 Issue: 7
Author(s): M. Salerno, E. Cenni, C. Fotia, S. Avnet, D. Granchi, F. Castelli, D. Micieli, R. Pignatello, M. Capulli, N. Rucci, A. Angelucci, A. Del Fattore, A. Teti, N. Zini, A. Giunti and N. Baldini
Affiliation:
Keywords: Bisphosphonates, bone targeting, doxorubicin, drug delivery system, nanoparticles, osteolysis, skeletal metastases.
Abstract: Bone metastases contribute to morbidity in patients with common cancers, and conventional therapy provides only palliation and can induce systemic side effects. The development of nanostructured delivery systems that combine carriers with bone-targeting molecules can potentially overcome the drawbacks presented by conventional approaches. We have recently developed biodegradable, biocompatible nanoparticles (NP) made of a conjugate between poly (D,Llactide- co-glycolic) acid and alendronate, suitable for systemic administration, and directly targeting the site of tumorinduced osteolysis. Here, we loaded NP with doxorubicin (DXR), and analyzed the in vitro and in vivo activity of the drug encapsulated in the carrier system. After confirming the intracellular uptake of DXR-loaded NP, we evaluated the antitumor effects in a panel of human cell lines, representative for primary or metastatic bone tumors, and in an orthotopic mouse model of breast cancer bone metastases. In vitro, both free DXR and DXR-loaded NP, (58-580 ng/mL) determined a significant dose-dependent growth inhibition of all cell lines. Similarly, both DXR-loaded NP and free DXR reduced the incidence of metastases in mice. Unloaded NP were ineffective, although both DXR-loaded and unloaded NP significantly reduced the osteoclast number at the tumor site (P = 0.014, P = 0.040, respectively), possibly as a consequence of alendronate activity. In summary, NP may act effectively as a delivery system of anticancer drugs to the bone, and deserve further evaluation for the treatment of bone tumors.
Export Options
About this article
Cite this article as:
Salerno M., Cenni E., Fotia C., Avnet S., Granchi D., Castelli F., Micieli D., Pignatello R., Capulli M., Rucci N., Angelucci A., Del Fattore A., Teti A., Zini N., Giunti A. and Baldini N., Bone-Targeted Doxorubicin-Loaded Nanoparticles as a Tool for the Treatment of Skeletal Metastases, Current Cancer Drug Targets 2010; 10 (7) . https://dx.doi.org/10.2174/156800910793605767
DOI https://dx.doi.org/10.2174/156800910793605767 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Assays for Identification of Hsp90 Inhibitors and Biochemical Methods for Discriminating their Mechanism of Action
Current Topics in Medicinal Chemistry Ischemic Neuronal Damage
Current Pharmaceutical Design A Survey of Deep Learning Based Methods in Medical Image Processing
Current Signal Transduction Therapy Investigation of Novel Chemical Inhibitors of Human Lysosomal Acid Lipase: Virtual Screening and Molecular Docking Studies
Combinatorial Chemistry & High Throughput Screening Understanding and Applying Personalized Therapeutics at Systems Level:Role for Translational Bioinformatics
Current Pharmacogenomics and Personalized Medicine The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB- 231 Cell Line
Current Cancer Drug Targets Glutamine, Glucose and other Fuels for Cancer
Current Pharmaceutical Design Significant Role of MUC1 in Development of Resistance to Currently Existing Anti-cancer Therapeutic Agents
Current Cancer Drug Targets Bioactive Peptides in Preventative Healthcare: An Overview of Bioactivities and Suggested Methods to Assess Potential Applications
Current Pharmaceutical Design HS-MMGKG: A Fast Multi-objective Harmony Search Algorithm for Two-locus Model Detection in GWAS
Current Bioinformatics Approaches for Developing Novel Microtubule Targeting Agents (MTAs) for Therapeutic Exploitation
Current Pharmaceutical Design Chemoprotection and Selection by Chemotherapy of Multidrug Resistance-associated Protein-1 (MRP1) Transduced Cells
Current Gene Therapy Graphene Oxide-Based Nanocarriers for Cancer Imaging and Drug Delivery
Current Pharmaceutical Design The ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) Trial: A Step Forward in the Treatment of Early Breast Cancer
Reviews on Recent Clinical Trials Potential Application of Biliverdin Reductase and its Fragments to Modulate insulin/IGF-1/MAPK/PI3-K Signaling Pathways in Therapeutic Settings
Current Drug Targets Raman, Infrared and NMR Spectroscopy: Advances in Structural, Conformational and Environmental Analysis
Combinatorial Chemistry & High Throughput Screening The Physiological Basis and Nutritional Function of Alpha-ketoglutarate
Current Protein & Peptide Science The Development of Hyaluronan as a Drug Transporter and Excipient for Chemotherapeutic Drugs
Current Pharmaceutical Biotechnology Fibroblast Growth Factor-Inducible 14: Multiple Roles in Tumor Metastasis
Current Molecular Medicine New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy
Current Cancer Drug Targets