Recent development of aptamer-nanomaterial assemblies witnesses a great success. However, the instability and off-target imperfection of the aptamer-nanomaterial assemblies still need to be improved for clinical theranostic development. Here, we show the aptamer sgc8-hybridized DNA dendrimers with engineering simplicity, robust biostability and target specificity. We introduced a trigger to a mixture of intelligently-designed oligonucleotides to initiate programmable hybridization/polymerization process that was controlled by substrates/byproducts equilibration cycles, yielding nick-sealed sgc8 DNA dendrimers after ligation with sgc8-Linkers. The molecular entity and biostability, targeting specificity and theranostic efficacy of the sgc8-DNA dendrimers were characterized by physicochemistry, molecular and cellular biology and in vivo models. The DNA dendrimers showed super-stability in FBS-containing culture medium or in serum for more than 36 h and were resistant to 100 ℃-annealing and physiological DNase. The sgc8-DNA dendrimers specifically distinguished target CCRF-CEM cells from the cognate ones, and bound to CCRF-CEM even in the presence of many interfering cells or in blood. The highly-branched dendrimers provided huge surface interfaces to load doxorubicin by G-C hybrids at a molar ratio over 350, and specifically delivered doxorubicin to nuclei of CCRF-CEM evidenced by DNA synthesis arrest and comet tail, thus preventing doxorubicin’s non-selective cytotoxicity. The sgc8-DNA dendrimers showed specific capturing of circulating CCRF-CEM cells and in vivo theranostic effects on implanted tumors. The novel and stable sgc8-DNA dendrimers with high pay-load may be best-suited for cancer theranostics.

适体-纳米材料组件的最新发展见证了巨大的成功。然而，适体-纳米材料组件的不稳定性和脱靶缺陷仍然需要改善，以用于临床治疗学发展。在这里，我们展示了具有工程简便性，强大的生物稳定性和靶标特异性的适体sgc8杂交的DNA树状聚合物。我们将触发器引入智能设计的寡核苷酸混合物中，以启动可编程的杂交/聚合过程，该过程受底物/副产物平衡循环的控制，与sgc8-Linker连接后可产生带有缺口的sgc8 DNA树状聚合物。通过理化，分子和细胞生物学以及体内模型对sgc8-DNA树状聚合物的分子实体和生物稳定性，靶向特异性和治疗诊断功效进行了表征。DNA树状分子在含FBS的培养基或血清中显示超过36小时的超稳定性，并且对100℃退火和生理DNase具有抗性。sgc8-DNA树状聚合物可将目标CCRF-CEM细胞与同类细胞区别开来，甚至在存在许多干扰细胞或血液中也可与CCRF-CEM结合。高支化的树枝状大分子提供了巨大的表面界面，可通过GC杂化剂以超过350的摩尔比负载阿霉素，并通过DNA合成阻滞和彗尾现象将阿霉素特异性地递送至CCRF-CEM的核中，从而防止了阿霉素的非选择性细胞毒性。sgc8-DNA树状聚合物显示出循环CCRF-CEM细胞的特异性捕获和体内对植入肿瘤的治疗效果。