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Published on: September 27, 2024
Biomimetic lipid nanoparticles mediated metabolic regulation and sonodynamic therapy for glioblastoma immunotherapy
Tiezheng Mo1, Faming Huang1, Yu Tian2
1School of Pharmacy, Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, Hainan provincial key laboratory of research and development on tropical herbs, International Joint Research Center of Human-machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Medical University, Haikou, 571199, China.
Abstract:
Regulation of the tumor microenvironment (TME) represents a promising strategy to enhance immunotherapy for glioblastoma (GBM) immunotherapy. Lactate dehydrogenase A (LDHA) is an attractive metabolic target for TME modulation. We developed cRGD-decorated, GBM cell membrane biomimetically modified lipid nanoparticles to co-deliver the sonosensitizer Ce6 and LDHA siRNA (Ce6/LDHA siRNA cRGD-BLNPs). The cRGD-cell membrane can endow LNPs with dual-targeting effect (cell membrane for homotypic targeting, cRGD for active targeting). Under ultrasound irradiation, immunogenic cell death (ICD) could be induced to release tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), thereby activating immune responses. Additionally, LDHA siRNA regulated lactic acid metabolism to reverse the immunosuppressive TME. This work provides a paradigm for lactic acid metabolism and ICD mediated GBM treatment, with potential clinical applicability for improving GBM immunotherapy.
