Nanoscale Metal-Organic Framework Confines Zinc-Phthalocyanine Photosensitizers for Enhanced Photodynamic Therapy.

Abstract

The performance of photodynamic therapy (PDT) depends on the solubility, pharmacokinetic behaviors, and photophysical properties of photosensitizers (PSs). However, highly conjugated PSs with strong reactive oxygen species (ROS) generation efficiency tend to have poor solubility and aggregate in aqueous environments, leading to suboptimal PDT performance. Here, we report a new strategy to load highly conjugated but poorly soluble zinc-phthalocyanine (ZnP) PSs in the pores of a Hf12-QC (QC = 2″,3'-dinitro-[1,1':4',1";4″,1'"-quaterphenyl]-4,4'"-dicarboxylate) nanoscale metal-organic framework to afford ZnP@Hf-QC with spatially confined ZnP PSs. ZnP@Hf-QC avoids aggregation-induced quenching of ZnP excited states to significantly enhance ROS generation upon light irradiation. With higher cellular uptake, enhanced ROS generation, and better biocompatibility, ZnP@Hf-QC mediated PDT exhibited an IC50 of 0.14 μM and achieved exceptional antitumor efficacy with >99% tumor growth inhibition and 80% cure rates on two murine colon cancer models.

• Authors: Taokun Luo, Geoffrey T Nash, Ziwan Xu, Xiaomin Jiang, Jianqiao Liu, Wenbin Lin
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 143 Issue 34 Pg. 13519-13524 (09 01 2021) ISSN: 1520-5126 [Electronic] United States
• PMID: 34424712 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biocompatible Materials
• Isoindoles
• Metal-Organic Frameworks
• Organometallic Compounds
• Photosensitizing Agents
• Reactive Oxygen Species
• Zinc Compounds
• Zn(II)-phthalocyanine

Topics

• Animals
• Biocompatible Materials (chemistry, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Isoindoles (chemistry)
• Lysosomes (metabolism)
• Metal-Organic Frameworks (chemistry)
• Mice
• Mice, Inbred BALB C
• Microscopy, Confocal
• Nanostructures (chemistry)
• Neoplasms (drug therapy, pathology)
• Organometallic Compounds (chemistry)
• Photochemotherapy
• Photosensitizing Agents (chemistry, metabolism, pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Transplantation, Heterologous
• Zinc Compounds (chemistry)