Abstract
Melanoma is one of the most malignant skin tumors,whose high invasion is generally associated with BRAF gene mutation.Although new chemotherapeutic drugs,such as vemurafenib,have been developed to inhibit the growth of melanoma,these drugs are usually administered intravenously or orally,result-ing in toxic side effects on major tissues and organs.Tetrahedral framework nucleic acids(tFNAs)are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease.In this study,we prepared tFNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of tFNAs(AS1411-tFNAs/vemurafenib).On one hand,AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro.Compared with free vemurafenib,AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells.On the other hand,AS 1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tis-sues.In vivo,transdermal delivery of AS1411-tFNAs/vemurafenib could inhibit the growth of human A375 melanoma,whose inhibiting effect was stronger than intravenous administration of vemurafenib.These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.
基金项目
国家重点研发计划(2019YFA0110600)
国家自然科学基金(81970916)
四川省科技计划(2022NSFSC0002)
Sichuan Province Youth Science and Tech-nology Innovation Team(2022JDTD0021)
Research and De-velop Program,West China Hospital of Stomatology Sichuan Uni-versity(RD03202302)
NETL
NSTL
万方数据