Tumor microenvironment and NIR laser dual-responsive release of berberine 9-O-pyrazole alkyl derivative loaded in graphene oxide nanosheets for chemo-photothermal synergetic cancer therapy.

A berberine 9-O-pyrazole alkyl derivative, a chemical compound (called B3) previously synthesized by our group, shows anti-cancer activity. However, B3 lacks targeting cytotoxicity to cancer cells, leading to obvious toxic side effects on normal cells. To solve this problem, here, we prepared a drug delivery system, namely, AS1411-GO/B3 for tumor targeting, in which nano-graphene oxide (GO) sheets were employed as the drug carrier, and the aptamer AS1411 was conjugated onto GO for tumor targeting. GO also had a photothermal effect, which helped the release of B3 from GO as well as the thermal cytotoxicity to cells. We found that the release of B3 could respond to acid conditions, indicating that the tumor intracellular environment could promote the release of B3, thus allowing it to perform chemotherapy effects. This system could also release B3 in response to photothermal heating, moreover, combined photothermal therapy and chemotherapy to improve the anticancer activity was achieved. This AS1411-GO/B3 platform with chemo-photothermal synergetic therapy provides a very promising treatment for tumors.