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Silver nanoparticles (SNPs), owing to their wide range of biomedical applications, have recently attracted remarkable interest for use in cancer nanomedicine. The present research work investigated the anticancer activity of phytosynthesized SNPs against human cancer cell lines. Phytosynthesis of SNPs was achieved by using an aqueous extract of Salacia chinensis (SC) bark as a green source to reduce silver nitrate to silver nanoparticles. Characterization of synthesized nanoparticles demonstrated a UV–visible peak at 443 nm, ζ-potential (zetasizer) of −25.6 ± 0.34 and particle size (transmission electron microscopy analysis) in the range of 40–80 nm, which validates formation of stable silver nanoparticles. The absence of cytotoxicity against normal human fibroblasts and blood erythrocytes confirms the biocompatible nature of green synthesized SNPs. In vitro anticancer assay demonstrated IC50 values of 6.31, 4.002, 5.228, 8.452, 14.37, 7.46, and 6.55 μg/mL against liver (Hep G2), lungs (L-132), pancreas (MIA-Pa-Ca-2), breast (MDA-MB-231), oral (KB cells), prostate (PC-3), and cervical (HeLa) cancer cell lines respectively, which confirms its potent anticancer action. The results of the present study give an experimental proof that the SC mediated green synthesized SNPs could serve as a promising anticancer agent to overcome limitations of existing conventional cancer chemotherapeutics.

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The destructive nature of the disease makes it difficult for clinicians to manage the condition. Hence, there is an urgent need to find new alternatives for HCC, as the role of conventional cytotoxic drugs has reached a plateau to control HCC associated mortality. Antioxidant compounds of plant origin with potential anti-tumor effect have been recognized as alternate modes in cancer treatment and chemoprevention. Resveratrol (RS) is a model natural nonflavonoid drug known for its anti-cancer activity. However, its clinical application is limited due to its poor bioavailability. The current research work aims to formulate, optimize, and characterize RS loaded cationic liposomes (RLs) for specific delivery in HCC. The optimized liposomes formulation (RL5) was spherical with a vesicle size (VS) of 145.78 ± 9.9 nm, ζ potential (ZP) of 38.03 ± 9.12 mV, and encapsulation efficiency (EE) of 78.14 ± 8.04%. In vitro cytotoxicity studies in HepG2 cells demonstrated an improved anti-cancer activity of RL5 in comparison with free RS. These outcomes were supported by a cell uptake study in HepG2 cells, in which RL5 exhibited a higher uptake than free RS. Furthermore, confocal images of HepG2 cells after 3 and 5 h of incubation showed higher internalization of coumarin 6 (C6) loaded liposomes (CL) as compared to those of the free C6. Pharmacokinetic and pharmacodynamic (prophylactic and therapeutic treatment modalities) studies were performed in N-nitrosodiethylamine (NDEA-carcinogen) induced HCC in rats. Pharmacokinetic evaluation of RL5 demonstrated increased localization of RS in cancerous liver tissues by 3.2- and 2.2-fold increase in AUC and Cmax, respectively, when compared to those of the free RS group. A pharmacodynamic investigation revealed a significant reduction in hepatocyte nodules in RL5 treated animals when compared to those of free RS. Further, on treatment with RL5, HCC-bearing rats showed a significant decrease in the liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin levels, γ-glutamyl transpeptidase, and α-fetoprotein), in comparison with that of the disease control group. Our findings were supported by histopathological analysis, and we were first to demonstrate that NDEA induced detrimental effect on rat livers was successfully reversed with the treatment of RL5 formulation. These results implied that delivery of RS loaded cationic liposomes substantially controlled the severity of HCC and that they can be considered as a promising nanocarrier in the management of HCC.