A major limitation of
tumor antiangiogenic
therapy is the pronounced off-target effect, which can lead to unavoidable injury in multiple organs. Ensuring sufficient delivery and controlled release of these
antiangiogenic agents at
tumor sites is crucial for realizing their clinical application. Here, we develop a smart
DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the
antiangiogenic agent,
endostar (Endo), into a reconfigurable
DNA framework nanotube (rDFN) that could recognize
tumor-overexpressed
nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the
tumor-targeting capability of Endo and maintain its efficient accumulation in
tumor tissues but also achieve on-demand release of Endo at
tumor sites via the specific
DNA aptamer for
tumor-overexpressed
nucleolin, named
AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and
tumor growth, while also providing effective protection against multiorgan
injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic
therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of
antiangiogenic agents.