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

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. <i>In vitro</i> 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.