Photodynamic therapy (PDT) has emerged as an alternative approach to chemotherapy and radiotherapy for cancer
treatment. The photosensitizer (PS) is perhaps the most critical component of PDT, and continues to be an area of
intense scientific research. Traditionally, PS molecules like porphyrins have dominated the field. Nevertheless, these PS
agents have several disadvantages, with low water solubility, poor light absorption, and reduced selectivity for targeted
tissues being some of the main drawbacks. Polysilsesquioxane (PSilQ) nanoparticles provide an interesting platform for
developing PS-loaded hybrid nanocarriers. Several advantages can be foreseen by using this platform such as carrying a
large payload of PS molecules; their surface and composition can be tailored to develop multifunctional systems (e.g.
target-specific); and due to their small size, nanoparticles can penetrate deep into tissues and be readily internalized by
cells. In this work, porphyrin-loaded PSilQ nanoparticles with a high payload of photosensitizers were synthesized,
characterized, and applied in vitro. The network of this nanomaterial is formed by porphyrin-based photosensitizers
chemically connected via a redox-responsive linker. Under reducing environment such as the one found in cancer cells
the nanoparticles can be degraded to efficiently release single photosensitizers in the cytoplasm. The platform was
further functionalized with polyethylene glycol (PEG) and folic acid as targeting ligand to improve its biocompatibility
and target specificity toward cancer cells overexpressing folate receptors. The effectiveness of this porphyrin-based
hybrid nanomaterial was successfully demonstrated in vitro using MDA-MB-231 breast cancer cell line.