State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, University of Science and Technology of China, Changchun, 130022, China.
Department of Radiology, Second Hospital of Jilin University, Changchun, 130041, China.
Angew Chem Int Ed Engl. 2019 May 6;58(19):6290-6294. doi: 10.1002/anie.201900884. Epub 2019 Apr 1.
Intracellular targeting has the same potential as tissue targeting to increase therapy efficacy, especially for drugs that are toxic to DNA. By adjusting intracellular traffic, we developed a novel direct-nucleus-delivery platform based on C N nanoparticles (NPs). Supramolecular interactions of C N NPs with the cell membrane enhanced cell uptake; abundant edge amino groups promoted fast and effective rupture of early endosomes; and the appropriate size of the NPs was also crucial for size-dependent nuclear entry. As a proof of concept, the platform was not only suitable for the effective delivery of molecular drugs/dyes (doxorubicin, hydroxycamptothecine, and propidium iodide) and MnO nanoparticles to the nucleus, but was also photoresponsive for nucleus-targeting photothermal therapy (PTT) and photodynamic therapy (PDT) to further greatly increase anticancer efficacy. This strategy might open the door to a new generation of nuclear-targeted enhanced anticancer therapy.
细胞内靶向与组织靶向一样具有提高治疗效果的潜力,特别是对于那些对 DNA 有毒的药物。通过调整细胞内运输,我们开发了一种基于 C N 纳米粒子(NPs)的新型直接细胞核递药平台。C N NPs 与细胞膜的超分子相互作用增强了细胞摄取;丰富的边缘氨基基团促进了早期内涵体的快速有效破裂;而 NPs 的适当大小对于尺寸依赖性核进入也是至关重要的。作为概念验证,该平台不仅适用于分子药物/染料(阿霉素、羟基喜树碱和碘化丙啶)和 MnO 纳米粒子的有效递送至细胞核,而且对核靶向光热治疗(PTT)和光动力治疗(PDT)具有光响应性,从而进一步大大提高了抗癌疗效。该策略可能为新一代的核靶向增强抗癌治疗开辟了道路。