Self‐Disassembling and Oxygen‐Generating Porphyrin‐Lipoprotein Nanoparticle for Targeted Glioblastoma Resection and Enhanced Photodynamic Therapy

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self‐disassembling porphyrin lipoprotein‐coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence‐guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self‐quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2) cores in PLCNP amplifies the fluorescence intensity of porphyrin‐lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low‐dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self‐disassembling and oxygen‐generating porphyrin‐lipoprotein nanoparticle may serve as a promising all‐in‐one nanotheranostic platform for guiding precise GBM excision and empowering post‐operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner. Porphyrin lipoprotein‐coated calcium peroxide nanoparticles (PLCNP) help realize the targeted accumulation, enhance porphyrin‐lipid fluorescence, and boost reactive oxygen species (ROS) generation. This all‐in‐one nanoplatform enables precise fluorescence‐guided GBM resection and enhances the post‐operative PDT effect via real‐time tumor fluorescence imaging and an ameliorated hypoxic tumor microenvironment. Created by BioRender.com.