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. 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 therapy (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape, the calcium peroxide (CaO 2 ) cores amplify the fluorescence intensity of porphyrin-lipids. Furthermore, the CaO 2 core has diminished tumor hypoxia and improves the PDT efficacy, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, PLCNP may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM elimination and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.