At present, fluorescent cystoscopy based on photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) has become a diagnostic approach for bladder tumors, which has been widely applied in Europe and U.S. However, photodynamic therapy (PDT) has not been widely adopted for bladder tumors due to various reasons.

To resolve these issues, based upon years of research on the application of laser in diagnosis and treatment of urinary diseases, He Dalin's team from Department of Urology of the First Affiliated Hospital of Xi 'an Jiaotong University (XJTU) cooperated with Zhang Penghui's team from Institute of Basic Medicine and Cancer of Chinese Academy of Sciences to jointly design a novel photosensitive material. They developed a nanocarrier (naming HAFeR) by encapsulating porphyrin sensitizer (H4TBP) and ferroptosis inducer (RSL3) in a metalorganic framework (MOF), which can synergistically activate ferroptosis and PDT. HAFeR can selectively interact with CD44 over-expressed on the surface of bladder tumor cells through hyaluronic acid in the outer layer, and be subsequently internalized via receptor-mediated endocytosis. After transferring inside the acidic lysosomes, the structure of HAFeR was decomposed to release the payloads, including porphyrin, Fe²⁺, Fe³⁺ and RSL3. Under 450 nm laser irradiation, theporphyrinproduced more massive ROS to induce drastic cell apoptosis than 630 nm laser due to higher photon energy and stronger absorption. Meanwhile, exogenous Fe3⁺catalyzed the conversion of H2O2 into O2 to alleviate tumor hypoxia via Fenton reaction, and also promoted RSL3 to downregulate GPX4 to induce lipid peroxidation (LPO), finally boosting ROS production for ferroptosis.

By combining apoptosis and ferroptosis, HAFeR showed potent toxicity to tumor cells and efficiently eradicated the tumor in MB49 tumor-bearing nude mice under 450 nm laser. In future transurethral resection of bladder tumor, the authors expect bulk bladder tumors can be directly resected by 450 nm laser surgery, and subtle lesions can be eradicated by PDT at low power mode, providing a promising strategy combining laser ablation and PDT within one laser system (Figure 1).

Relevant results were published as an Article entitled Photoactivatable Metal Organic Framework for Synergistic Ferroptosis and Photodynamic Therapy Using 450 nm Laser in Chemical Engineering Journal. Our hospital is the first affiliation, Chen Yuhang, a doctoral student from XJTU Health Science Center is the first author, Professor He Dalin and Professor Guo Peng from our hospital and Professor Zhang Penghui are the co-corresponding authors of this article. This work was supported by Natural Science Foundation of China and Key Research and Development Program of Shaanxi.

Figure 1 Schematic illustration of HAFeR MOFs mediated hypoxia-tolerant and labile iron pool 

(LIP)-enhancing synergistic ferroptosis and photodynamic therapy.

Article link: https://doi.org/10.1016/j.cej.2022.140438