Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral-Framework Nucleic-Acid Nanostructures Functionalized with Osteogenic Growth Peptide.

Abstract

As major complications of chemoradiotherapy, myelosuppression and hematopoietic‐system damage severely affect immunologic function and can delay or even terminate treatment for cancer patients. Although several specific cytokines have been used for hematopoiesis recovery, their effect is limited, and they may increase the risk of tumor recurrence. In this study, osteogenic growth peptide functionalized tetrahedral framework nucleic‐acid nanostructures (OGP‐tFNAs) are prepared; they combine the positive hematopoiesis stimulating effect of OGP and the drug carrying function of tFNAs. The potential of OGP‐tFNAs for hematopoietic stimulation and microenvironment regulation is investigated. It is shown that OGP‐tFNAs can protect bone marrow stromal cells from 5‐fluorouracil (5‐FU)‐induced DNA damage and apoptosis. OGP‐tFNAs pretreatment activates the extracellularly regulated protein kinase signal and downregulates apoptosis‐related proteins. OGP‐tFNAs also alleviate the chemotherapy‐induced inhibition of hematopoiesis‐related cytokine expression, which is crucial for hematopoiesis reconstitution. In conclusion, OGP‐tFNAs can protect hematopoietic cells and their microenvironment from chemotherapy‐induced injuries and myelosuppression, while promoting hematopoiesis regeneration.