Anisamide-targeted PEGylated gold nanoparticles designed to target prostate cancer mediate: Enhanced systemic exposure of siRNA, tumour growth suppression and a synergistic therapeutic response in combination with paclitaxel in mice
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Authors: Luan, Xue; Rahme, Kamil; Cong, Zhongcheng; Wang, Limei; Zou, Yifang; He, Yan; Yang, Hao; Holmes, Justin D.; O'Driscoll, Caitriona M.; Guo, Jianfeng
Abstract
Small interfering RNA (siRNA) has recently illustrated therapeutic potential for malignant disorders. However, the clinical application of siRNA-based therapeutics is significantly retarded by the paucity of successful delivery systems. Recently, multifunctional gold nanoparticles (AuNPs) as non-viral delivery carriers have shown promise for transporting chemotherapeutics, proteins/peptides, and genes. In this study, AuNPs capped with polyethylenimine (PEI) and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of positively charged anisamide-targeted PEGylated AuNPs (namely Au-PEI-PEG-AA). The anisamide-targeted AuNPs effectively complexed siRNA via electrostatic interaction, and the resultant complex (Au-110-PEI-PEG(5000)-AA.siRNA) illustrated favourable physicochemical characteristics, including particle size, surface charge, and stability. In vitro, anisamide-targeted AuNPs selectively bound to human prostate cancer PC 3 cells, inducing efficient endosomal escape of siRNA, and effective downregulation of the RelA gene. In vivo, prolonged systemic exposure of siRNA was achieved by anisamide-targeted AuNPs resulting in significant tumour growth suppression in a PC3 xenograft mouse model without an increase in toxicity. In addition, a combination of siRNA-mediated NF-kappa B knockdown using anisamide-targeted AuNPs with Paclitaxel produced a synergistic therapeutic response, thus providing a promising therapeutic strategy for the treatment of prostate cancer.
Expression and Clinical Significance of Translation Regulatory Long Non-Coding RNA 1 (TRERNA1) in Ependymomas
PATHOLOGY & ONCOLOGY RESEARCH
Authors: Malgulwar, Prit Benny; Nambirajan, Aruna; Singh, Manmohan; Suri, Vaishali; Sarkar, Chitra; Sharma, Mehar Chand
Abstract
Long noncoding RNAs (lncRNA) have emerged as vital molecules governing epithelial-to-mesenchymal transition (EMT) in cancers. Translation regulatory RNA 1 (TRERNA1) is one such lncRNA known to enhance the transcriptional activity of the EMT-transcription factor, Snail. We have previously demonstrated differential upregulation of EMT-transcription factors and cadherin switching across various clinico-pathologic-molecular subclasses of ependymomas (EPN). With an aim to analyze the correlation between the expression ofTRERNA1in EPNs, we performed gene expression analysis forTRERNA1on 75 Grade II/III EPNs and correlated with tumor site,C11orf95-RELAfusions, age, MIB-1 proliferative indices, and outcome wherever available. Upregulation of gene expression levels ofTRERNA1was seen in intracranial EPNs, with highest expression levels in pediatric posterior fossa EPNs. HighTRERNA1expression was found associated with higher proliferative indices (p = 0.034) and shorter progression free survival (p = 0.002). Our study, for the first time, demonstrates an association betweenTRERNA1expressions and pediatric posterior fossa EPNs. Further in-vivo and in-vitro studies are required to confirm these findings and evaluateTRERNA1as a novel biomarker and potential therapeutic target in childhood PF-EPNs.