DNA Framework-Programmed Ligand Positioning to Modulate the Targeting Performance
2022
Gao, Mengqiu | Han, Zhihao | Zhou, Li | Li, Ping | Xu, Haoran | Gu, Yueqing | Ma, Yi
Effective targeting of nanomedicine is still an intricacy since unsatisfactory clinical trial feedback demonstrated their inadequate concentration at the desired area. However, the regulatory effect of ligand-modification patterns on the targeting effect has not been surveyed yet. Based on the superior spatial addressability of DNA frame structures, herein DNA tetrahedrons were used as templates for site-specific modification of targeting ligands. In this work, nanovectors with homogeneous ligand-modification patterns, including various valence of ligands and the precisely controlled distance between ligands at the nanoscale, were established for the first time. In vitro and in vivo targeting performance studies found that merely relying on the augment of the ligand quantity exhibited a confined promotion effect on the targeting efficiency. Notably, the space distance between ligands displayed a more important role in reforming the targeting effect, and the largest ligand distance (approximately 156.55 Å) pattern exhibited an optimal targeting effect and prominently cytostatic activity toward tumor cells. Generally, the survey of ligand-modification patterns on nanovectors provided a valid guidance to direct the optimization of nanomedicine.
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