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  3. A blood-brain barrier-penetrating nanoreactor for tumor microenvironment modulation, precise MR imaging and synergistic therapy of glioma

A blood-brain barrier-penetrating nanoreactor for tumor microenvironment modulation, precise MR imaging and synergistic therapy of glioma

  • Int J Pharm X. 2025 Nov 17:10:100448. doi: 10.1016/j.ijpx.2025.100448.
Peipei Dou 1 2,  Liang Chen 1,  Yiyang Xie 1,  Wenbei Xu 1,  Xinran Zhang 1,  Xiaomei Deng 1,  Haiqing Xu 3,  Jingran Li 4,  Vincent Kawuribi 1,  Shaohui Zheng 1 2,  Kai Xu 1 2,  Jing Zhang 1 2
Affiliations

Affiliations

  • 1 School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China.
  • 2 Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China.
  • 3 UWE college, Hainan Medical University, Hainan 571199, China.
  • 4 The University of Waikato Joint Institute, Hangzhou City University, Hangzhou 310015, China.
PMID: 41362442 DOI: 10.1016/j.ijpx.2025.100448
Abstract

Nanomaterials-based theranostic strategy have emerged as innovative techniques for gliomas treatment. However, the existence of blood-brain barrier (BBB) hinders efficient drug delivery to glioma, and the hypoxic condition of tumor microenvironment (TME) significantly reduces therapeutic efficacy. Thus, in this study, we developed a novel Reactive Oxygen Species (ROS)-generating nanoplatform responsive to the TME. This platform utilized mesoporous PtNi nanoparticles (NPs) as carriers, loaded with chelated gadolinium porphyrin (Gd-HMME), to enable combined sonodynamic and chemodynamic therapy under magnetic resonance imaging (MRI) guidance. Employing a transferrin (Tf)-mediated trans-BBB strategy, Tf-PtNi@Gd-HMME-PEG (TPGP) precisely targeted and penetrated glioma tissues, facilitating T1-weighted enhanced imaging of tumor regions. The MRI enhancement signal achieved was 1.64-fold of the control group. Concurrently, the intrinsic acoustic sensitivity and enzyme-like catalytic activity of TPGP produce substantial ROS under ultrasound stimulation. These ROS interact with hydrogen peroxide in the TME to generate toxic free radicals, collectively acting on tumor cells to deliver a dual assault via sonodynamic and chemodynamic mechanisms to effectively inhibit tumor growth and ameliorate the tumor microenvironment. This study underscores the potential of TPGP as a multifunctional nanoplatform for targeted glioma therapy, combining diagnostic imaging with synergistic therapy to overcome the BBB and hypoxic TME.

Keywords

Blood-brain barrier penetration; Magnetic resonance imaging; Nanozymes; Synergistic CDT/SDT; Tumor microenvironment modulation.

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