Nanotherapy silencing the interleukin‐8 gene produces regression of prostate cancer by inhibition of angiogenesis
Autor: | Haotian Sun, Supriya D. Mahajan, Bindukumar Nair, Hanguang Zhang, Jessica L. Reynolds, Donald E. Sykes, Chih-Kuang Chen, Kailash C. Chadha, Katelyn D. Bothwell, Steven G. Turowski, Stanley A. Schwartz, Mukund Seshadri, Chong Cheng, Ravikumar Aalinkeel |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Small interfering RNA Angiogenesis Polyesters medicine.medical_treatment Immunology Cell Mice Nude Biocompatible Materials Metastasis Mice 03 medical and health sciences Prostate cancer 0302 clinical medicine Cell Line Tumor Animals Humans Immunology and Allergy Medicine Gene silencing Interleukin 8 Neoplasm Metastasis RNA Small Interfering Mice Knockout Mice Inbred BALB C Neovascularization Pathologic business.industry Interleukin-8 Prostatic Neoplasms Original Articles medicine.disease Xenograft Model Antitumor Assays Tumor Burden 030104 developmental biology medicine.anatomical_structure Cytokine 030220 oncology & carcinogenesis Cancer research Nanoparticles business |
Zdroj: | Immunology. 148:387-406 |
ISSN: | 1365-2567 0019-2805 |
Popis: | Interleukin-8 (IL-8) is a pro-angiogenic cytokine associated with aggressive prostate cancer (CaP). We detected high levels of IL-8 in sera from patients with CaP compared with healthy controls and patients with benign prostatic hypertrophy. This study examines the role of IL-8 in the pathogenesis of metastatic prostate cancer. We developed a biocompatible, cationic polylactide (CPLA) nanocarrier to complex with and efficiently deliver IL-8 small interfering RNA (siRNA) to CaP cells in vitro and in vivo. CPLA IL-8 siRNA nanocomplexes (nanoplexes) protect siRNA from rapid degradation, are non-toxic, have a prolonged lifetime in circulation, and their net positive charge facilitates penetration of cell membranes and subsequent intracellular trafficking. Administration of CPLA IL-8 siRNA nanoplexes to immunodeficient mice bearing human CaP tumours produced significant antitumour activities with no adverse effects. Systemic (intravenous) or local intra-tumour administration of IL-8 siRNA nanoplexes resulted in significant inhibition of CaP growth. Magnetic resonance imaging and ultrasonography of experimental animals demonstrated reduction of tumour perfusion in vivo following nanoplex treatment. Staining of tumour sections for CD31 confirmed significant damage to tumour neovasculature after nanoplex therapy. These studies demonstrate the efficacy of IL-8 siRNA nanotherapy for advanced, treatment-resistant human CaP. |
Databáze: | OpenAIRE |
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