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

Author:

Chen Yaoxing1ORCID,Ma Yuxiao2,Shi Kexin1,Chen Huan1,Han Xiao1,Wei Chenxuan1,Lyu Yingqi1,Huang Yukun1,Yu Renhe1,Song Yun3,Song Qingxiang1,Jiang Jiyao2,Feng Junfeng2,Lin Yingying2,Chen Jun4,Chen Hongzhuan15,Zheng Gang16,Gao Xiaoling1,Jiang Gan1ORCID

Affiliation:

1. Department of Pharmacology and Chemical Biology State Key Laboratory of Systems Medicine for Cancer Shanghai Universities Collaborative Innovation Center for Translational Medicine Shanghai Jiao Tong University School of Medicine 280 South Chongqing Road Shanghai 200025 China

2. Brain Injury Centre Renji Hospital School of Medicine Shanghai Jiao Tong University 1630 Dongfang Road Shanghai 200127 China

3. Department of Pharmacy Huashan Hospital Fudan University 12 Middle Wulumuqi Road Shanghai 200040 China

4. Key Laboratory of Smart Drug Delivery Ministry of Education School of Pharmacy Fudan University 826 Zhangheng Road Shanghai 201203 China

5. Institute of Interdisciplinary Integrative Biomedical Research Shuguang Hospital Shanghai University of Traditional Chinese Medicine 1200 Cailun Road Shanghai 201210 China

6. Department of Medical Biophysics University of Toronto 101 College Street Toronto Ontario M5G 1L7 Canada

Abstract

AbstractThe 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.

Funder

National Natural Science Foundation of China

Shanghai Science and Technology Development Foundation

Shanghai Rising-Star Program

National Key Research and Development Program of China

Publisher

Wiley

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