Photosensitizer-based metal-organic frameworks for highly effective photodynamic therapy

Highlights: • Photosensitizer-based metal-organic frameworks in photodynamic therapy are reviewed • PS-based MOFs prevent self-aggregation of PS and improve PDT outcomes • Metal presence enables parallel approaches that improve PDT results • Drug loading in the highly porous MOFs structure allows for combined therapies • PSs structured in MOFs are highly effective in PDT compared to their free forms Photodynamic therapy (PDT) uses a photosensitizer, molecular oxygen, and visible light as an alternative clinical protocol against located malignant tumors and other diseases. More recently, PDT has been combined to immunotherapy as a promising option to treat metastatic cancer. However, previous generations of photosensitizers (PSs) revealed clinical difficulties such as long-term skin photosensitivity (first generation), the need for drug delivery vehicles (second generation), and intracellular self-aggregation (third generation), which have generated a somewhat confusing scenario in PDT approaches and evolution. Recently, metal-organic frameworks (MOFs) with exceptionally high PS loading as a building unit of MOF framework have emerged as fourth-generation PS and presented outstanding outcomes under pre-clinical studies. For PS-based MOFs, the inorganic building unit (metal ions/clusters) plays an important role as a coadjuvant in PDT to alleviate hypoxia, to decrease antioxidant species, to yield ROS, or to act as a contrast agent for imaging-guided therapy. In this review, we intend to carry out a broad update on the recent history and the characteristics of PS-based MOFs from basic chemistry to the structure relationship with biological application in PDT. The details and variables that result in different photophysics, size, and morphology, are discussed. Also, we present an overview of the achievements on the pre-clinical assays in combination with other strategies, including alleviating hypoxia in solid tumors, chemotherapy, and the most recent immunotherapy for cancer.