Rational design of ROS-responsive nanocarriers for targeted X-ray-induced photodynamic therapy and cascaded chemotherapy of intracranial glioblastoma
Glioblastoma (GBM) is the most lethal primary intracranial tumor because of its high invasiveness and recurrence. Therefore, nanocarriers with blood–brain barrier (BBB) penetration and transcranial-controlled drug release and activation are rather attractive options for glioblastoma treatment. Herein, we designed a multifunctional nanocarrier (T-TKNPVP) that combined targeted X-ray-induced photodynamic therapy (X-PDT) and cascaded reactive oxygen species (ROS)-boosted chemotherapy. The T-TKNPVP loaded with verteporfin (VP) and paclitaxel (PTX) was self-assembled from an angiopep-2 (Ang) peptide, functionalized Ang-PEG-DSPE and ROS-sensitive PEG-TK-PTX conjugate. After systemic injection, the T-TKNPVP efficiently crossed the BBB and targeted the GBM cells via receptor-mediated transcytosis. Upon X-ray irradiation, they can generate a certain amount of ROS, which not only induces X-PDT but also locoregionally activates PTX release and action by cleaving the TK bridged bonds. As evidenced by 9.4 T MRI and other experiments, such nanocarriers offer significant growth inhibition of GBM in situ and prolong the survival times of U87-MG tumor-bearing mice. Taken together, the designed T-TKNPVP provided an alternative avenue for realizing transcranial X-PDT and X-ray-activated chemotherapy for targeted and locoregional GBM treatment in vivo.
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