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

in Advanced materials (Deerfield Beach, Fla.) by Yaoxing Chen, Yuxiao Ma, Kexin Shi, Huan Chen, Xiao Han, Chenxuan Wei, Yingqi Lyu, Yukun Huang, Renhe Yu, Yun Song, Qingxiang Song, Jiyao Jiang, Junfeng Feng, Yingying Lin, Jun Chen, Hongzhuan Chen, Gang Zheng, Xiaoling Gao, Gan Jiang

TLDR

  • The study creates a special kind of nanoparticle that can help doctors remove a type of brain tumor called glioblastoma multiform (GBM). The nanoparticle can help doctors see where the tumor is located during surgery and can also help doctors treat the remaining tumor after surgery. The study shows that the nanoparticle is effective at reducing the amount of tumor left and improving the treatment of the remaining tumor. The study suggests that this nanoparticle could be used in other brain tumors and that more research is needed to make sure it is safe and effective for humans.

Abstract

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 (CaO) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaOcore 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.

Overview

  • The study aims to develop a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) to target glioblastoma multiform (GBM) via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. The study tests the hypothesis that the incorporation of calcium peroxide (CaO) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid and reduces tumor hypoxia, improving the PDT efficacy of PLCNP and providing a clinically applicable strategy to combat GBM in a safe and effective manner.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions, including the use of PLCNP versus traditional surgical intervention and PDT. The results show that PLCNP significantly reduces GBM residual and improves PDT efficacy compared to traditional methods. The study also identifies that the incorporation of CaO cores in PLCNP enhances lysosome escape efficiency and reduces self-quenching, leading to improved fluorescence intensity and reduced tumor hypoxia.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they provide a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT. The study suggests future research directions, including the optimization of PLCNP design and the exploration of its potential for use in other brain tumors. The study also highlights the need for further clinical trials to evaluate the safety and efficacy of PLCNP in human patients.
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