Self-Propulsion of Biomimetic Nanomotors Promotes Diffusion and Convection Transport for Enhanced Radiotherapy in Solid Glioblastoma

Abstract

As a principal adjuvant therapy for glioblastoma (GBM), radiotherapy (RT) is instrumental in extending patient survival. Radiosensitizers could enhance the cytotoxic effects of radiation on tumor cells. However, their accumulation and penetration are significantly hindered by the blood-brain barrier (BBB) and weak convection and diffusion due to elevated interstitial pressure and the dense extracellular matrix within GBM, which reduces the effectiveness of RT. To maximize the radiosensitizing efficiency, it is imperative to develop a delivery system capable of crossing the BBB, specifically targeting GBM, and penetrating the center of the GBM. We propose utilizing cell membrane camouflage to achieve BBB crossing and tumor targeting and the self-propulsion ability of nanomotors to promote diffusion and overcome convection within GBM, thereby facilitating deep tumor penetration. We first clarify that the hollow structure with an opening exhibits a stronger propulsive force than the Janus structure under identical conditions. Subsequently, we developed a facile method to prepare nanomotors featuring a hollow structure with an opening. By camouflaging the nanomotors with hybrid cell membranes with BBB-crossing and tumor-targeting capabilities, we create biomimetic nanomotors (Bio-motors). Results show our Bio-motors possess enhanced diffusion capacity and achieve deep penetration under reverse pressure gradients, which also effectively traverse the BBB, target GBM, and penetrate deeply within the tumor. Notably, the Bio-motors enhance radiosensitivity and inhibit GBM growth, thereby prolonging the median survival of GBM-bearing mice. Our Bio-motors will significantly boost RT efficacy for GBM patients and could be readily adapted into versatile carriers for tumor therapy due to the modular design.

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