TY - JOUR
T1 - Engineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis
AU - Hao, Xinyan
AU - Tang, Yucheng
AU - Xu, Wenjie
AU - Wang, Ming
AU - Liu, Jiayi
AU - Li, Yongjiang
AU - He, Jun
AU - Peng, Yanjin
AU - Sun, Pengcheng
AU - Liao, Dehua
AU - Hu, Xiongbin
AU - Tang, Tiantian
AU - Zhou, Min
AU - Han, Ruyue
AU - Wang, Jiemin
AU - Conde, João
AU - Xiang, Daxiong
AU - Wu, Junyong
N1 - © 2025. The Author(s).
PY - 2025/1/15
Y1 - 2025/1/15
N2 - 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.
AB - 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.
KW - Pyroptosis/drug effects
KW - Cisplatin/pharmacology
KW - Glioblastoma/drug therapy
KW - Animals
KW - Humans
KW - Mice
KW - Cell Line, Tumor
KW - Polyphenols/pharmacology
KW - Immunotherapy/methods
KW - Antineoplastic Agents/pharmacology
KW - Brain Neoplasms/drug therapy
KW - Biomimetic Materials/chemistry
KW - Mice, Inbred BALB C
KW - Mice, Nude
KW - B7-H1 Antigen/metabolism
KW - Programmed Cell Death 1 Receptor/metabolism
KW - Biomimetics/methods
U2 - 10.1186/s12951-025-03091-w
DO - 10.1186/s12951-025-03091-w
M3 - Article
C2 - 39810130
SN - 1477-3155
VL - 23
SP - 14
JO - Journal of Nanobiotechnology
JF - Journal of Nanobiotechnology
IS - 1
ER -