Journal Article

Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis

Hao, Xinyan, Sun, Pengcheng, Han, Ruyue, Xiang, Daxiong, He, Jun, Conde, João, Wu, Junyong, Xu, Wenjie, Wang, Ming, Peng, Yanjin, Tang, Tiantian, Wang, Jiemin, Zhou, Min, Hu, Xiongbin, Liao, Dehua, Tang, Yucheng, Liu, Jiayi, Li, Yongjiang

2025

Overview

Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation. For the effective delivery of CDDP, the CDDP-polyphenol nanocomplexes were prepared, and catalase and copper ions were incorporated to fortify structural integrity, enhance glutathione (GSH) responsiveness, and ameliorate tumor hypoxia. Additionally, BV2 microglial cells were engineered to overexpress programmed death-1 (PD-1), and the membrane is employed for nanocomplex coating, effectively blocking the CDDP-induced upregulation of programmed death ligand 1 (PD-L1). Furthermore, the angiopep-2 peptide was modified to efficiently cross the blood brain barrier and specifically target GBM cells. In vitro analyses confirmed potent cytotoxicity and characteristic induction of pyroptosis. In vivo assays corroborated the enhancement of tumor targeting, culminating in an obvious suppression of tumor proliferation. A notable activation of immune cells was observed within tumors and lymph nodes, indicative of a synergistic effect of chemotherapy and immunotherapy, underscoring its potential as a safe and efficacious therapeutic strategy against GBM.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animals / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Apoptosis / B7-H1 Antigen - metabolism / Biocompatibility / Biomimetic Materials - chemistry / Biomimetic Materials - pharmacology / Biomimetics / Biomimetics/methods / Biotechnology / Blood-brain barrier / Brain cancer / Brain Neoplasms - drug therapy / Brain tumors / Cancer / Caspase-3 / Catalase / Cell activation / Cell death / Cell Line / Cell Line, Tumor / Cell proliferation / Chemistry / Chemistry and Materials Science / Chemo-immunotherapy / Chemotherapy / Cisplatin / Cisplatin - chemistry / Cisplatin - pharmacology / Cytotoxicity / Dosage and administration / Drug delivery systems / Drug resistance / Drug therapy / Drugs / Efficiency / Electrons / Flow cytometry / Glioblastoma / Glioblastoma - drug therapy / Glioblastoma - pathology / Glioblastoma multiforme / Glioma / Glutathione / Health aspects / Humans / Hypoxia / Immune response / Immune system / Immunotherapy / Immunotherapy - methods / Inbred BALB C / Localization / Lymph nodes / Membranes / Mice / Microglia / Microscopy / Molecular Medicine / Nanocomposites / Nanoparticles / Nanoparticles - chemistry / Nanotechnology / Nude / Particle size / PD-1 protein / PD-L1 protein / Peptides / Pharmaceutical research / Polyethylene glycol / Polyphenols / Polyphenols/pharmacology / Programmed Cell Death 1 Receptor/metabolism / Programmed death-1 / Proteins / Pyroptosis / Pyroptosis - drug effects / Spectrum analysis / Structural integrity / Survival analysis / Synergistic effect / Technology application / Tumor / Tumors / Vehicles