Metabolic cooperation via gap junctional intercellular comtransduced with HSVtk via either retrovirus or adenovirus munication (GJIC) is an important mechanism of the vectors. This augmentation of bystander effect could also bystander effect in gene therapy using the herpes simplex be seen in vivo. HSVtk-transduced tumors in mice treated virus thymidine kinase/ganciclovir (HSVtk/GCV) 'prodrug' with the combination of GCV and retinoids were signifisystem. Since retinoids have been reported to increase cantly smaller than those treated with GCV or retinoids GJIC by induction of connexin expression, we hypothesalone. These results provide evidence that retinoids can ized that these compounds could be used to augment the augment the efficiency of cell killing with the HSVtk/GCV HSVtk/GCV bystander effect. Addition of all-trans retinoic system by enhancing bystander effects and may thus be acid increased GJIC in tumor cell lines, augmented a promising new approach to improve responses in gene expression of connexin 43, and was associated with more therapy utilizing the HSVtk/GCV system to treat tumors or efficient GCV-induced in vitro bystander killing in cells vascular restenosis.

Breast cancer is the most common and deadly cancer among women worldwide. Currently, nanotechnology-based drug delivery systems are useful for cancer treatment; however, strategic planning is critical in order to enhance the anti-cancer properties and reduce the side effects of cancer therapy. Here, we designed multifunctional gold nanoparticles (AuNPs) conjugated with two anti-cancer drugs, TGF-β1 antibody and methotrexate, and a cancer-targeting molecule, folic acid. First, optimum size and shape of AuNPs was selected by the highest uptake of AuNPs by MDA-MB-231, a metastatic human breast cancer cell line. It was 100 nm spherical AuNPs (S-AuNPs) that were used for further studies. A fixed amount (900 μl) of S-AuNP (3.8 × 10(8) particles/ml) was conjugated with folic acid-BSA or methotrexate-BSA. Methotrexate on S-AuNP induced cellular toxicity and the optimum amount of methotrexate-BSA (2.83 mM) was 500 μl. Uptake of S-AuNPs was enhanced by folate conjugation that binds to folate receptors overexpressed by MDA-MB-231 and the optimum uptake was at 500 μl of folic acid-BSA (2.83 mM). TGF-β1 antibody on S-AuNP reduced extracellular TGF-β1 of cancer cells by 30%. Due to their efficacy and tunable properties, we anticipate numerous clinical applications of multifunctional gold nanospheres in treating breast cancer.

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