Objectives
Gold nanoparticles (AuNPs) are used to deliver drugs and therapeutic small molecule inhibitors to cancer cells. Evidence shows that AuNPs coated with nuclear localization sequence can cross the nuclear membrane and induce cellular apoptosis. To determine the therapeutic role of AuNPs, we compared two nanoconstructs conjugated to doxorubicin (DOX) through pH‐sensitive and pH‐resistant linkers.
Materials and Methods
We tested DOX nanoconjugates' cytotoxicity, cellular and nuclear uptake in oral squamous cell carcinoma cell line. Furthermore, we evaluated the therapeutic effect of pH‐sensitive and pH‐resistant DOX bioconjugates in hamster buccal pouch carcinoma model.
Results
Our data indicate that pH‐resistant and pH‐sensitive DOX‐nanoconjugates were equally localized in cancer cells, but the pH‐resistant DOX nanoparticles were more localized in the nuclei inducing a 2‐fold increase in the apoptotic effect compared with the pH‐sensitive DOX nanoparticles. Our in vivo results show significantly higher tumor shrinkage and survival rates in animals treated with DOX pH‐resistant AuNPs compared with pH‐sensitive ones.
Conclusion
Our findings suggest that AuNPs enhance the cytotoxic effect against cancer cells in addition to acting as drug carriers. DOX pH‐resistant AuNPs enhanced accumulation of AuNPs in cancer cells’ nuclei inducing a significant cellular apoptosis which was confirmed using in vitro and in vivo experiments without deleterious effects on blood cell count.
Due to the therapeutic importance of microbial pigments, these pigments are receiving the attention of researchers. In this present study 60 isolates were isolated from sediments of Abu-Qir coast of the Mediterranean sea, Alexandria, Egypt, out of which 12 were considered as pigmented actinomycetes. Streptomyces sp. W4 was characterized by small round green pigmented colonies when grown on starch-casein agar medium. The green pigment was extracted using a mixture of acetone-methanol (7:3 v/v). The antimicrobial, antioxidant, antiviral, and anticancer activities of the green pigment produced by Streptomyces sp.W4 were investigated. The pigment was characterized using FTIR, Raman spectroscopy, EDX and GC–MS. The results revealed that the pigment has antibacterial and antifungal activity and also showed inhibition of HAV 78% but its antiviral activity against the Adenovirus was weak. The results proved the safety of the pigment toward normal cells and anticancer activity against three different cancer cell lines HepG-2 (liver cancer cell line), A549 (lung cancer cell line), and PAN1 (pancreas cancer cell line). The pigment was combined with 9 antibiotics and then tested against the Gram-negative bacterium Enterococcus faecalis using disc diffusion bioassay. LEV showed an antagonistic effect, while CXM and CIP showed a synergistic effect.
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