Rational design of ROS-responsive nanocarriers for targeted X-ray-induced photodynamic therapy and cascaded chemotherapy of intracranial glioblastoma

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Glioblastoma (GBM) is a highly invasive and recurrent brain tumor, necessitating advanced treatment strategies.
• Current treatments face challenges with blood-brain barrier (BBB) penetration and targeted drug delivery.
• Nanocarriers offer potential for enhanced BBB crossing and controlled therapeutic agent release.

Purpose of the Study:

• To design and evaluate a multifunctional nanocarrier for targeted glioblastoma treatment.
• To combine X-ray-induced photodynamic therapy (X-PDT) with chemotherapy for synergistic effects.
• To achieve transcranial drug delivery and activation for improved therapeutic outcomes.

Main Methods:

• Self-assembly of a nanocarrier (T-^TKNP_VP) using angiopep-2 peptide, functionalized PEG-DSPE, and a ROS-sensitive PEG-TK-PTX conjugate.
• Loading nanocarriers with verteporfin (VP) for X-PDT and paclitaxel (PTX) for chemotherapy.
• In vivo assessment of BBB penetration, GBM targeting, X-PDT/chemotherapy activation via X-ray irradiation, and therapeutic efficacy using MRI and survival studies.

Main Results:

• The T-^TKNP_VP nanocarriers successfully penetrated the BBB and targeted GBM cells via receptor-mediated transcytosis.
• X-ray irradiation triggered ROS generation, activating both X-PDT and locoregional PTX release and chemotherapy.
• Significant in situ GBM growth inhibition and prolonged survival in U87-MG tumor-bearing mice were observed.

Conclusions:

• The developed T-^TKNP_VP nanocarrier system provides an effective platform for transcranial X-PDT and X-ray-activated chemotherapy.
• This approach offers a promising strategy for targeted and locoregional glioblastoma treatment.
• The nanocarrier demonstrates potential for overcoming BBB limitations in brain tumor therapy.