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

Autor: Jianfeng Guo, Hao Yang, Yan He, Xue Luan, Yifang Zou, Kamil Rahme, Caitriona M. O'Driscoll, Limei Wang, Zhongcheng Cong, Justin D. Holmes
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Small interfering RNA
Paclitaxel
Pharmaceutical Science
Metal Nanoparticles
Mice
Nude
02 engineering and technology
030226 pharmacology & pharmacy
Polyethylene Glycols
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Downregulation and upregulation
In vivo
Cell Line
Tumor
Animals
Humans
Polyethyleneimine
RNA
Small Interfering
Combination therapy
Non-viral siRNA delivery
Polyethylenimine
Gene knockdown
Mice
Inbred BALB C
Prostate cancer
Cancer gene therapy
Gene Transfer Techniques
NF-kappa B
Prostatic Neoplasms
General Medicine
021001 nanoscience & nanotechnology
Antineoplastic Agents
Phytogenic
Combined Modality Therapy
Xenograft Model Antitumor Assays
In vitro
Treatment Outcome
chemistry
Colloidal gold
Gene Knockdown Techniques
Benzamides
Cancer research
Gold
0210 nano-technology
Biotechnology
Popis: 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 (Au110-PEI-PEG5000-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-κB knockdown using anisamide-targeted AuNPs with Paclitaxel produced a synergistic therapeutic response, thus providing a promising therapeutic strategy for the treatment of prostate cancer.
Databáze: OpenAIRE
Externí odkaz: