Lexiscan Research Articles

Autocatalytic, Brain Tumor‐Targeting Delivery of Bardoxolone Methyl Self‐Assembled Nanoparticles for Glioblastoma Treatment

Glioblastoma multiforme (GBM) is a formidable cancer to treat due to the lack of effective drugs that can also efficiently cross the blood–brain barrier (BBB). Herein, a novel strategy involving the synthesis of p28 peptide‐conjugated, lexiscan (LEX)‐loaded, bardoxolone methyl (BM) self‐assembled nanoparticles, designated as p28‐LBM NPs, is introduced. These NPs are designed to overcome the dual challenges of effectively killing GBM cells and efficiently penetrating the brain. The p28 peptide is chosen for targeted delivery to brain tumors, and LEX is employed to enhance drug penetration across the BBB. The successful penetration of brain tumors by the p28‐LBM NPs after intravenous administration is demonstrated, with BM delivered as part of the NPs significantly inhibiting GBM tumor growth and extending the survival of mice with tumors. In conclusion, the p28‐LBM NPs present a promising approach for GBM treatment, with potential for effective and safe clinical applications in the future.

Lexiscan can open the blood-brain barrier temporarily and reversibly

Objective To evaluate the opening level and optimal time window of the blood-brain barrier induced by adenosine A2 receptor agonist (Lexiscan) via dynamic enhanced MRI. Methods Twenty New Zealand white rabbits were divided into experiment group (group A, n=10) and control group (group B, n=10). Rabbits in group A were injected with Lexiscan and rabbits in group B were injected with physiological salt via ear vein, then the coronary scanning was performed. Contrast enhanced MRI was performed at different time points (5, 10, 15, 20 min, and then every 10 min, until 2 h) following the infusion of Gd-diethylene triamine pentaacetic acid (DTPA). The signal intensity (SI) of region of interest (ROI) was measured and the percent enhancement of SI was calculated. Evens blue staining results in brain tissues were observed. Pair t test was used to analyze the data. Results The percent enhancement of SI in group A significantly increased to (40.93±3.70)% at 5 min, reached the maximum of (43.03±3.62)% at 30 min, slowly decreased until 50 min, and got to a stable level at almost 80 min. At each time point, the percent enhancement of SI in group A was significantly higher than that in group B (t values: 6.88-20.28, all P<0.05). The staining was evident in group A. Conclusions Lexiscan can open blood-brain barrier temporarily and reversibly, and the optimal opening time window is 10-50 min post-injection. Key words: Blood-brain barrier; Adenosine A2 receptor agonists; Magnetic resonance imaging; Gadolinium DTPA; Rabbits