(366v) A Highly Efficient MOF-Based Photosensitizer for the Treatment of Capillary Malformations

Metal-organic frameworks (MOFs), as a large group of nanomaterial, have been thoroughly studied and widely used in many fields. They are formed by strong bonding between inorganic and organic unit with ultrahigh porosity and specific surface area. We are committed to developing and enhancing the application of nanomaterials like MOFs in various fields, especially in the medical field where nanotechnology has a promising application prospect.

Recently, we have developed a MOF-based photosensitizer (PS) with good efficacy against vascular diseases. Capillary malformations (CM) are the most common type of vascular malformation, and the most common type of CM is port-wine stains (PWS). It mainly affects the skin and mucous membranes of a person, and in severe cases it can lead to the development of Sturge-Weber syndrome or cancer. Currently, there are two main known pathogenic mechanisms of CM, a mutation in the GNAQ gene (R183Q) in cells and the coexistence of EphB1 and efnB2 receptors that disrupt the normal interactions between endothelial cells, leading to progressive vasodilation in PWS. Photodynamic therapy (PDT) is an effective treatment based on the local activation of intracellular PS to induce the production of reactive oxygen species (ROS), causing chemical damage that leads to cell death. Although there are now some effective PS drugs on the market, the accompanying biotoxicity remains a concern. And currently common PS are still dominated by small molecules, which rely on passive targeting strategy to accumulate in targeting cells and tissues, but this targeting effect is not sufficient enough, and still have unforeseen side effects on normal cells and tissues.

Herein, we developed an efficient and safe PS drug based on porphyrin-based MOFs. Specific metal ions can be combined with hematoporphyrin monomethyl ethers (HMME) to synthesize amorphous MOFs structures by a one-pot method. HMME combining with metal zirconium (Zr-HF) has shown better dispersion and homogeneity than other metal like Fe and Mn. Several different kinds of Zr-HF all have lower toxicity than HMME molecules in the cells with worse PDT performance. These HMME-MOFs exhibit good PDT effects while greatly reducing the cytotoxicity associated with conventional small molecule PS. Meanwhile, surface modification of MOFs has also been done which effectively enhanced the targeting effect of PS drug. Monocyte cell membranes have been used to encapsulate the MOFs which can actively target the endothelial cell with GNAQ (R183Q) mutation through the interaction of proteins on the surface of the cell membrane.

In conclusion, by combining existing small-molecule PS with metal ions to synthesize new MOF-based PS, it is possible to reduce drug cytotoxicity and enhance targeting effect while ensuring PDT performance. This idea can be applied not only to vascular and skin diseases, but also to more life-threatening diseases such as cancer by photodynamic or acoustic therapy.