Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice

Abstract

Short interfering RNA (siRNA) possesses special ability of silencing specific gene. To increase siRNA stability, transportation and its uptake by tumor cells, effective delivery to the appropriate target cells is a major challenge of siRNA-based therapy. In the present study, an effective, safe and biocompatible survivin siRNA encapsulated, GalNAc decorated PEGylated PLGA nanoconjugates (NCs) viz., GalNAc@PEG@siRNA-PLGA were engineered and their synergistic antitumor efficacy was evaluated for targeted delivery in HCC bearing experimental mice. GalNAc@PEG@siRNA-PLGA NCs were characterized for size, bioavailability, toxicity and biocompatibility. Their antitumor potential was evaluated considering gene silencing, apoptosis, histopathology and survival of treated mice. Exceptional accumulation of hepatocytes, reduction in survivin expression and prominent regression in tumor size confirmed the ASGPR-mediated uptake of ligand-anchored NCs and silencing of survivin gene in a targeted manner. Increased DNA fragmentation and potential modulation of caspase-3, Bax and Bcl-2 factors specified the induction of apoptosis that helped in significant inhibition of HCC progression. The potential synchronous and tumor selective delivery of versatile NCs indicated the effective payloads towards the target site, increased apoptosis in cancer cells and improved survival of treated animals.

Potential cytotoxicity of silver nanoparticles: Stimulation of autophagy and mitochondrial dysfunction in cardiac cells

“…Zeta-potential was measured according to the Smoluchowski equation. AgNPs were dispersed in an aqueous solution and the measurements were performed in triplicates on undiluted samples at 25 °C by Zeta Nano ZS (Malvern Instruments Ltd., Worcestershire, UK) ( Khan et al, 2019 ).…”

Pomegranate peel induced biogenic synthesis of silver nanoparticles and their multifaceted potential against intracellular pathogen and cancer

“…PDI values were analyzed by the Cumulant analysis method. The measurements were performed in triplicates on undiluted samples at 25 °C ( Khan et al, 2019 ).…”

“…Nanoparticles are being considered as an eminent component of the widely accelerating field of nanotechnology embodying various real-world applications. The burgeoning nano-based therapeutic interventions offer intriguing approaches that hold potentials for the treatment of myriads of debilitating diseases ( Khan et al, 2013 , Khan et al, 2019 ). In the realms of metal nanoparticles; silver, gold, copper and zinc oxide have been demonstrated as wonder alternative therapeutic agents.…”

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

“…Authors have reported a successful siRNA inhibition of targeted gene expression and the induction of cancer cell apoptosis, while also detecting a reduction in tumor size (Figure 2b ). [ 49 , 50 , 51 , 52 , 53 ] Furthermore, the effect of siRNAs in neurological disorders has been studied to effectively inhibit targeted gene expression in the central nervous system by specific gene silencing. [ 54 , 55 ] Additionally, GalNAc‐siRNA conjugates are exploited for efficient siRNA delivery to liver hepatocytes, inducing targeted gene silencing while guaranteeing the duration of the effect.…”