Radiation-synthesized naringin-loaded PEG-Au nanocomposite induces autophagy and suppresses hepatocellular carcinoma in rats via modulation of the PI3K/Akt/mTOR downstream beclin-1/ATG2A pathway

Abstract Background Naringin, a flavonoid compound found in citrus fruits, possesses valuable anticancer properties. However, its potential application in cancer treatment is limited by poor bioavailability and pharmacokinetics at tumor sites. To address this, this study investigates the therapeutic potential of a radiation-synthesized naringin-loaded PEG-coated gold nanocomposite (NAR-PEG-AuNPs) in the treatment of hepatocellular carcinoma (HCC) induced in rats by diethylnitrosamine (DEN). Methods A total of 90 male albino rats were divided into five groups, including controls, NAR-PEG-AuNPs alone, DEN-induced HCC, and DEN-treated rats receiving NAR-PEG-AuNPs post-induction. The nanocomposite was characterized and administered over an 8-week period following cancer induction. Our multi-faceted approach assessed the redox tone and the modulation of key signaling pathways—PI3K, Akt, and mTOR—via RT-PCR, along with autophagy indicators Beclin-1 and Atg2a via RT-PCR, and apoptotic markers Bax and Bcl-2 through ELISA. Additionally, tumor proliferation was evaluated by PCNA immunohistochemistry. Results The particle size of NAR-PEG-AuNPS was determined by transmission electron microscopy, Ultraviolet-visible spectrophotometer and Fourier-transform infrared spectroscopy. Results demonstrated that NAR-PEG-AuNPs significantly mitigated tumor progression, modulating autophagy and apoptosis pathways and reducing cellular proliferation. Conclusions These findings suggest that the nanocomposite exerts its anti-tumor effects by targeting critical molecular mechanisms involved in hepatocarcinogenesis. The study highlights the potential of nanotechnology-enhanced phytochemicals as promising adjuncts or alternatives in HCC therapy. Importantly, NAR-PEG-AuNPS showed no cytotoxic effects on normal cells. Combining NAR-PEG-AuNPS with chemotherapy drugs could present a novel approach for treating human cancers.