ABSTRACT
This study evaluated the delivery efficiency and antitumor effects of the intrapulmonary administration of antitumor small interfering ribonucleic acid (siRNA)-containing nanoparticles to mice with metastatic lung tumor. Fluorescence-labeled, siRNA-containing nanoparticles were administered using Liquid MicroSprayer® to mice with metastatic lung tumors induced by the murine melanoma cell line B16F10. Fluorescent signals in the whole lung and in the tumor region following the intrapulmonary administration of siRNA-containing nanoparticles were stronger than those following intravenous administration. The intrapulmonary administration of nanoparticles containing a mixture of siRNA against MDM2, c-Myc, and vascular endothelial growth factor (VEGF) significantly improved survival and prolonged the survival of mice with metastatic lung tumor. In addition, after the intrapulmonary or intravenous administration of the mixture, the activity levels of interleukin-6 and -12, markers of systemic toxicity, were similar to those of nontreatment. These results indicate that the antitumor siRNA-containing nanoparticles were delivered efficiently and specifically to tumor cells, effectively silencing the oncogenes in the lung metastasis without any significant systemic toxicity.
Subject(s)
Drug Delivery Systems , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Melanoma, Experimental/pathology , RNA, Small Interfering/administration & dosage , Animals , Cell Line, Tumor , Drug Delivery Systems/instrumentation , Female , Lung Neoplasms/genetics , Mice, Inbred C57BL , Nanoparticles/chemistry , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-myc/genetics , RNA, Small Interfering/therapeutic use , RNAi Therapeutics/instrumentation , Vascular Endothelial Growth Factor A/geneticsABSTRACT
El neuroblastoma (NB) es el tumor sólido más común en niños y adolescentes y representa hasta un 15% de la muerte infantil asociada al cáncer. Tiene su origen en el sistema nervioso simpático y su comportamiento puede llegar a ser muy agresivo y no responder a los tratamientos actuales. En esta revisión se recogen nuevas alternativas terapéuticas basadas en la epigenética, es decir, en moduladores de la expresión génica como los microRNAs y su potencial aplicación clínica en NB
Neuroblastoma (NB) is the most common solid tumour in children and adolescents, and accounts for up to 15% of all cancer deaths in this group. It originates in the sympathetic nervous system, and its behaviour can be very aggressive and become resistant to current treatments. A review is presented, summarising the new alternative therapies based on epigenetics, i.e., modulators of gene expression, such as microRNAs and their potential application in the clinical practice of NB treatment
