Engineering prodrug nanoparticles for targeted therapy in heterogeneous glioblastoma

Zhang，Xuefeng1,2; Guo，Qing3,4; Zhao，Zongren5; Cheng，Peng4; Wu，Anhua3; Liu，Hongmei1,2

2023-10-15

10.1016/j.cej.2023.145557

Chemical Engineering Journal   Impact Factor & Quartile

1385-8947

1873-3212

Glioblastoma (GBM) microenvironment heterogeneity poses a major challenge to GBM therapy. Glioma stem cells (GSCs) and tumor-associated macrophages (TAMs) are important elements in the GBM microenvironment and are crucial for malignant progression. Here, we constructed prodrug nanoparticles (A-PER-p(TMZ)/Clo) containing perifosine (Akt inhibitors), an ester bond-linked poly-temozolomide (poly(TMZ)) prodrug, and clodronate (Clo) for combined approach to TAMs depletion, GSCs eradication, and activation inhibition of GBM. A-PER-p(TMZ)/Clo treatment in a mouse model of intracranial GBM significantly inhibited tumor growth and markedly extended survival. These findings suggest that A-PER-p(TMZ)/Clo provides a new strategy for therapeutic targeting of the heterogeneous glioma microenvironment.

Akt inhibitors Glioblastoma Glioma stem cells Heterogeneity Tumor-associated macrophages

SCI

English

First

Booz Allen Foundation[2011225034];Booz Allen Foundation[2020BS117];Booz Allen Foundation[81872054];Booz Allen Foundation[82203672];

Engineering

Engineering, Environmental ; Engineering, Chemical

WOS:001070991000001

ELSEVIER SCIENCE SA

ENGINEERING

2-s2.0-85170250240

Scopus

1.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,No. 1088, Xueyuan Avenue,518055,China
2.Institute of Nervous System Diseases,Xuzhou Medical University,Xuzhou,No. 84 Huaihai Xi Road,221002,China
3.Department of Neurosurgery,Shengjing Hospital of China Medical University,Shenyang,No. 36, Sanhao Street, Heping District, Liaoning,110004,China
4.Department of Neurosurgery,The First Hospital of China Medical University,Shenyang,No. 155, Nanjing Bei Street,110001,China
5.Department of Neurosurgery,Affiliated Huaian Hospital of Xuzhou Medical University,No. 62, Huaihai Bei Road,223002,China

Zhang，Xuefeng,Guo，Qing,Zhao，Zongren,et al. Engineering prodrug nanoparticles for targeted therapy in heterogeneous glioblastoma[J]. Chemical Engineering Journal,2023,474.

Zhang，Xuefeng,Guo，Qing,Zhao，Zongren,Cheng，Peng,Wu，Anhua,&Liu，Hongmei.(2023).Engineering prodrug nanoparticles for targeted therapy in heterogeneous glioblastoma.Chemical Engineering Journal,474.

Zhang，Xuefeng,et al."Engineering prodrug nanoparticles for targeted therapy in heterogeneous glioblastoma".Chemical Engineering Journal 474(2023).