Dual Delivery of Light/Prodrug Nanoparticles Using Tumor-Implantable Micro Light-Emitting Diode on an Optofluidic System for Combinational Glioma Treatment

Abstract

Glioma is a highly lethal tumor with a poor prognosis, in which the presence of the blood-brain barrier (BBB) and skull significantly limits treatment options. To address this, a tumor-implantable optofluidic system (LED-SC), consisting of a microsized LED (microLED) and a microsyringe chip (SC), is proposed to deliver both light and prodrug nanoparticles (PNPs) directly to brain glioma. The LED-SC combines microLED and SC to enable intratumoral administration of light and PNPs for chemophotodynamic therapy. PNPs, self-assembled nanoparticles of verteporfin (VPF)-doxorubicin (DOX) prodrug, are cleaved by the enzyme cathepsin B, releasing active drugs specifically within tumor cells. In vitro studies show that PNPs are taken up by glioma cells and exhibit enhanced cytotoxicity under light irradiation. The PNPs-loaded LED-SC can be implanted into glioma, wherein PNPs are slowly diffused through the tumor, bypassing the BBB, and it also ensures effective light delivery in glioma beneath the skull, boosting chemo-photodynamic therapy. In glioma mouse models, PNP-loaded LED-SC implantation showed a 3.9-fold improvement in PNP delivery efficiency over intravenous administration, leading to better drug distribution and therapeutic results. The PNPs-loaded LED-SC offers a promising and minimally invasive solution for glioma treatment, overcoming the barriers of the BBB and skull while reducing systemic toxicity.