A Multifunctional DNA Nano-scorpion For Highly Efficient Targeted Delivery Of Mrna Therapeutics

Cancer is gradually becoming a hidden threat to human health.The traditional treatments of cancer are mainly through surgery,radiotherapy and chemotherapy.Although these treatments have saved countless lives,they are also faced with many challenges such as surgical contraindications and poor prognosis.Therefore,new methods for cancer treatment are still important areas that need urgent exploration and research.In recent years,efficient and precise gene therapy methods are playing an important role in cancer treatment.Herein,a multifunctional DNA nano-scorpion nanostructure（termed AptDzy-DNS）functioned with aptamers and DNAzyme is developed for highly efficient targeted delivery of mRNA therapeutics in gene therapy.The head of the designed AptDzy-DNS is self-assembled with specific aptamers as“scorpion stingers”for targeting tumor cell,and Mg²⁺-dependent DNAzymes on its two arms are as“scorpion pincers”for cleaving mRNA into fragments.In the process of gene therapy,the cleaved mRNA fails to be translated into corresponding protein.Following,the downregulation protein can block cancer cell growth and realize highly efficient targeted therapies.The results demonstrate that the multifunctional AptDzy-DNS can not only achieve targeted cancer cell discrimination of two breast cancer cells（SK-BR-3 and MDA-MB-231）,but also decrease mRNA and protein expression level by RT-PCR and Western blot assay.The decrease shows a therapeutic effect on targeted cancer cells.Therefore,this study provides a novel idea for the targeted therapy of cancer cells,and also shows a great potential for the application of AptDzy-DNS in the targeted treatment of human cancer.