ORIGINAL ARTICLE Raptinal silver nanoparticles: new therapeutic advances in hepatocellular carcinoma mouse model Heba Taha 1 & Nourhan Elfar 2 & Hesham Haffez 1,3 & Zeineb A. Hassan 1 Received: 18 June 2020 /Accepted: 4 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Raptinal is a novel antineoplastic agent that induces an expeditious intrinsic apoptotic pathway, in addition to the shutdown of mitochondrial function for cancerous cells, because of silver nanoparticles (AgNPs) that have been shown to provide a worthy approach to overcome tumors. In this study, Both Raptinal and Raptinal-loaded silver nanoparticles (AgNPs) were tested as the first time in hepatocellular carcinoma–induced mice to evaluate its efficacy and targeting to HCC. Seventy-two albino male mice of comparable age were classified into six groups; early stage of HCC was induced using diethyl nitrosamine (DEN)/carbon tetrachloride (CCL4). Liver function was assessed in all groups using ALT, AST, total bilirubin, and alpha-fetoprotein (AFP) as well as histopathological examination. Quantitative gene expression of key apoptotic gene markers p53, cytochrome c, and caspase 3 was assessed in all liver homogenates. The results showed that Raptinal-loaded AgNPs group had significant increase in both apoptotic genes of cytochrome c and Caspase 3 at P = 0.0001 compared with Raptinal-free drug group. AFP levels were significantly decreased in Raptinal-loaded AgNPs group compared with both Raptinal-free drug and HCC groups at P = 0.0001. Degenerative changes in the hepatocytes with focal necrosis and inflammatory cell infiltration in histopathology confirm the biochemical analysis. Our study is considered one of the first studies using Raptinal in vivo. Moreover, it showed that Raptinal and/or the combination between Raptinal and AgNPs showed a promising therapeutic agent in treating early HCC. Keywords Raptinal . Silver nanoparticles . Alpha-fetoprotein . Apoptosis . Hepatocellular carcinoma Introduction Hepatocellular carcinoma (HCC) is the largest recorded hepatic carcinogenesis (Kasprzak and Adamek 2018). It is considered the second most frequent trigger concerning cancer-related mor- tality worldwide, and sixth in rank concerning new cases in Egypt (Yang et al. 2011). The International Agency for Research reported that deaths caused by cancer worldwide will be increased up to 13 million by 2030 (Siegel et al. 2014). Similarly to other cancer types, the treatment and prognosis of HCC change depend on some given factors such as tumor his- tology, size, presence of metastasis, and patient general health (Radwan et al. 2019). Alpha-fetoprotein (AFP) has long been known to correlate with HCC prognosis and has historically played a role as a widely serological marker in diagnosis and monitoring of HCC (Bai et al. 2017). However, there are consequences of limited HCC curative such as doxorubicin and sorafenib of first-line chemotherapy treatment that leads to failure in the initial responses in clinical phase (Deng 2015). Hence, there is Highlights • The first study that evaluated the efficacy of Raptinal as a novel drug in the treatment of HCC in an animal model • Discover the potential effect of Raptinal-loaded AgNPs in early HCC in vivo • Comparison between efficacy of Raptinal and Raptinal-loaded AgNPs as rapid and potent inducers of apoptosis Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01973-4) contains supplementary material, which is available to authorized users. * Heba Taha heba.taha@pharm.helwan.edu.eg; hebatahasharaf@yahoo.com 1 Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo 11795, Egypt 2 Egyptian Drug Authority (EDA), Ministry of Health and Population, Cairo 11567, Egypt 3 Helwan Structural Biology Center for Excellence , Helwan University , Cairo 11795, Egypt Naunyn-Schmiedeberg's Archives of Pharmacology https://doi.org/10.1007/s00210-020-01973-4