Collaborative Innovation Center of Biomedical Functional Materials of Jiangsu Province, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.
Nano Lett. 2024 Aug 28;24(34):10605-10613. doi: 10.1021/acs.nanolett.4c02817. Epub 2024 Aug 15.
A metal-organic frameworks (MOFs)-in-MOF nanovehicle (160 nm), which was constructed with newly prepared ultrasmall Cu(I)Cu(II)-BTC MOFs (UCMs, 2.95 nm) loaded with doxorubicin (DOX) and a nuclear localization signal (NLS) peptide as multicores (UCMDNs) and ZIF-8 as the shell MOF, was proposed to cross layers of biological barriers with adaptive size evolution capacity for achieving efficient nucleus-targeted drug delivery. It first enhanced tumor tissue penetration through its larger nanosize effect. Then the acidic tumor environment made the ZIF-8 shell degrade, releasing small-sized UCMDNs to enter into the cell and into the nucleus under the guidance of NLS. Furthermore, due to the distinct surface structural characteristics of UCMs, UCMDNs remained stable in the cytoplasm and collapsed in the nucleus due to the DOX-DNA interaction to deliver DOX precisely. It showed superior performance in the nucleus-directed delivery of DOX (delivery efficiency up to 56.7%) and a high tumor growth inhibition rate (96.4%), offering promising prospects in tumor chemotherapy.
一种金属-有机骨架（MOFs）-在-MOF 纳米载体（160nm），由新制备的超小的 Cu(I)Cu(II)-BTC MOFs（UCMs，2.95nm）负载阿霉素（DOX）和核定位信号（NLS）肽作为多核（UCMDNs）和 ZIF-8 作为壳 MOF 构建而成，具有自适应尺寸演变能力，可穿越生物屏障层，实现高效的核靶向药物传递。它首先通过更大的纳米尺寸效应增强肿瘤组织穿透性。然后，酸性肿瘤环境使 ZIF-8 壳降解，在 NLS 的引导下，释放出小尺寸的 UCMDNs 进入细胞并进入细胞核。此外，由于 UCMs 的独特表面结构特征，UCMDNs 在细胞质中保持稳定，而在核内由于 DOX-DNA 相互作用而崩溃，从而精确传递 DOX。它在 DOX 的核定向传递中表现出优异的性能（传递效率高达 56.7%）和高肿瘤生长抑制率（96.4%），为肿瘤化疗提供了有前途的前景。
