Meng Yingcai, Huang Jiaxin, Ding Jinsong, Yan Bohua, Li Yong, Gao Xiang, Zhou Wenhu
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China; Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China.
J Colloid Interface Sci. 2023 May;637:441-452. doi: 10.1016/j.jcis.2023.01.089. Epub 2023 Jan 23.
Manganese oxide nanomaterials (MONs) are emerging as a type of highly promising nanomaterials for diseases diagnosis, and surface modification is the basis for colloidal stability and targeting delivery of the nanomaterials. Here, we report the in-situ functionalization of MnO with DNA through a biomineralization process. Using adsorption-oxidation method, DNA templated Mn precursor to biomineralize into nano-cubic seed, followed by the growth of MnO to form cube/nanosheet hybrid nanostructure. Among four types of DNA homopolymers, poly-thymine (poly-T) was found to stably attach on MnO surface to resist various biological displacements (phosphate, serum, and complementary DNA). Capitalized on this finding, a di-block DNA was rationally designed, in which the poly-T block stably anchored on MnO surface, while the AS1411 aptamer block was not only an active ligand for tumor targeting delivery, but also a carrier for photosensitizer (Ce6) loading. Upon targeting delivery into tumor cells, the MnO acted as catalase-mimic nanozyme for oxygenation to sensitize photodynamic therapy, and the released Mn triggered chemodynamic therapy via Fenton-like reaction, achieving synergistic anti-tumor effect with full biocompatibility. This work provides a simple yet robust strategy to functionalize metal oxides nanomaterials for biological applications via DNA-templated biomineralization.
氧化锰纳米材料（MONs）正成为一类在疾病诊断方面极具潜力的纳米材料，而表面修饰是纳米材料胶体稳定性和靶向递送的基础。在此，我们报道了通过生物矿化过程实现DNA对MnO的原位功能化。采用吸附 - 氧化法，DNA模板化的Mn前驱体生物矿化形成纳米立方晶种，随后MnO生长形成立方/纳米片杂化纳米结构。在四种类型的DNA均聚物中，发现聚胸腺嘧啶（poly - T）能稳定附着在MnO表面，以抵抗各种生物置换（磷酸盐、血清和互补DNA）。基于这一发现，合理设计了一种双嵌段DNA，其中poly - T嵌段稳定锚定在MnO表面，而AS1411适配体嵌段不仅是用于肿瘤靶向递送的活性配体，还是用于负载光敏剂（Ce6）的载体。在靶向递送至肿瘤细胞后，MnO作为过氧化氢酶模拟纳米酶进行氧化以敏化光动力疗法，释放的Mn通过类芬顿反应引发化学动力疗法，实现具有完全生物相容性的协同抗肿瘤效果。这项工作提供了一种简单而稳健的策略，通过DNA模板化生物矿化对金属氧化物纳米材料进行功能化以用于生物应用。
