DNA-Functionalized Porphyrinic Metal-Organic Framework-Based Drug Delivery System for Targeted Bimodal Cancer Therapy

• Published in: Journal of medicinal chemistry 2023-11, Vol.66 (22), p.15370-15379
• Main Authors: Zhao, Qiu-Ge, Zhou, Yun-Jie, Cao, Dong-Xiao, Tang, An-Na, Kong, De-Ming
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; DNA; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Carriers - chemistry; Drug Delivery Systems; Drug Liberation; Humans; Metal-Organic Frameworks - chemistry; Metal-Organic Frameworks - therapeutic use; Neoplasms - drug therapy
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.3c01479

A DNA-functionalized porphyrinic MOF (porMOF) drug delivery system was successfully constructed. porMOF as a photosensitizer and drug delivery carrier can integrate photodynamic therapy (PDT) and chemotherapy. Via the strong coordination interaction between the zirconium cluster of porMOF and the terminal phosphate group of DNA, the stable modification of the DNA layer on the porMOF surface is achieved. Meanwhile, the introduction of C/G-rich base pairs into the DNA double-stranded structure provides more binding sites of chemotherapeutic drug doxorubicin (DOX). AS1411, an aptamer of nucleolin proteins that are overexpressed by cancer cells, is introduced in the double-stranded terminal, which can endow the nanosystem with the ability to selectively recognize cancer cells. C-rich sequences in DNA double strands form an i-motif structure under acidic conditions to promote the highly efficient release of DOX in cancer cells. and experiments demonstrate that the synergistic PDT/chemotherapy modality achieves highly efficient cancer cell killing and tumor ablation without undesirable side effects.