A dual-functional nanomedicine combining fluorinated antisense oligonucleotide with chemotherapeutic drug for synergistic gene-chemo tumor treatment

The synergistic anti-tumor therapy based on chemotherapeutic drugs and gene drugs has become a new direction of tumor treatment. However, the significantly distinct physicochemical properties and the unbalanced coordinate proportion of chemotherapeutic and genetic drugs limit the actual therapeutic efficiency of the combined drug delivery strategy. Herein, we developed a simple method to self-assemble the fluorine atom-modified antisense oligonucleotide (2'F-G1319) with chemotherapeutic pirarubicin (THP) to form the carrier-free nanomedicines (2'F-G1319/THP NMs), which could efficaciously achieve the synergistic gene therapy and chemotherapy. In this study, 2'F-G1319 and THP could be self-assembled to form uniform nanoparticles through enhanced intermolecular interactions after G1319 was modified with the fluorine atom. Both in-vitro and in-vivo experiments verified that 2'F-G1319/THP NMs exhibited significant synergistic anti-tumor effects with high biostability and biocompatibility. Owing to the simple and universal synthesis process, our constructed self-assembled nanomedicine provides a promising opportunity for the wide applications of nanomedicines and is expected to realize more effective synergistic anti-tumor therapy without the addition of non-therapeutic excipients.