An iron-based metal-organic framework nanoplatform for enhanced ferroptosis and oridonin delivery as a comprehensive antitumor strategy.

Ferroptosis is a recently discovered pathway for regulated cell death pathway. However, its efficacy is affected by limited iron content and intracellular ion homeostasis. Here, we designed a metal-organic framework (MOF)-based nanoplatform that incorporates calcium peroxide (CaO2) and oridonin (ORI). This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis, thereby enhancing ferroptosis therapy. Fused cell membranes (FM) were used to modify nanoparticles (ORI@CaO2@Fe-TCPP, NPs) to produce FM@ORI@CaO2@Fe-TCPP (FM@NPs). The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously, working in tandem with Fe3+ to induce ferroptosis. Photodynamic therapy (PDT) guided by porphyrin (TCPP) significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species (ROS). This self-amplifying strategy promoted robust ferroptosis, which could work synergistically with FM-mediated immunotherapy. In vivo experiments showed that FM@NPs inhibited 91.57% of melanoma cells within six days, a rate 5.6 times higher than chemotherapy alone. FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity. Thus, this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.

Phototherapeutic effect of transformable peptides containing pheophorbide a on colorectal cancer.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have attracted research interest for their noninvasive nature and selective treatment of tumor tissues. They are effective through the generation of reactive oxygen species (ROS) or heat. Nevertheless, several problems, including low bioavailability and long-lasting cutaneous photosensitivity, have limited their clinical application. In this study, we reported an in situ self-assembly strategy that could improve various biological properties of the photosensitizer in vivo. A photosensitizer connected to a receptor-mediated smart peptide can self-assemble into nanoparticles (NPs) under the force of hydrophobic interaction and then transform into a nanofibrillar network after attaching to the tumor cell surface with the help of the ß-sheet-forming peptide KLVFF. The supramolecular structural changes deeply affected the PDT and PTT properties of the photosensitizer on tumors. After being aggregated into the nanostructure, the water solubility and targeting ability of the photosensitizer was ameliorated. Moreover, the improvement of the photothermal conversion efficiency, ROS generation, and tumor retention followed the formation of nanofibrils (NFs). This self-assembly strategy showed the ability of supramolecular nanofibrils to improve the bioavailability of photosensitizers, which provides a new potential treatment avenue for various cancer therapies.