Chemo-Photodynamic Glioma Treatment Using Implantable Micro-LED and Drug Delivery System

Nano-sized drug delivery systems have been developed for targeted delivery of anticancer drugs, yet their systemic administration efficacy remains limited. To enhance targeting efficiency and minimize toxicity, we developed a combined approach utilizing a tumor-implantable micro-syringe chip (MSC) with a needle-type implantable micro-LED device for glioma treatment. The MSC, equipped with a 2μL drug reservoir, enables precise intratumoral delivery of pro-apoptotic anticancer prodrugs (SMAC-P-FRRG-DOX) encapsulated in optimized liposome nanoparticles (ApoLNPs), ensuring uniform drug distribution and enhanced tumor targeting. Complementing this, the micro-LED device, consisting of four small LEDs at the needle tip, can be implanted into the glioma core without craniotomy, delivering deep-tissue light irradiation. This approach overcomes the challenge of inadequate light penetration, crucial for photodynamic therapy. The device activates cathepsin B-responsive prodrug nanoparticles (PNPs) composed of doxorubicin, verteporfin, and a cathepsin B-cleavable peptide linker. PNPs remain inactive under normal conditions but release therapeutic agents specifically in cathepsin B-overexpressed glioma tissues. In vitro cellular assays showed that irradiated PNPs exhibit synergistic cytotoxicity in cancer cells while sparing normal cells. In vivo studies in tumor-bearing mice demonstrated high tumor accumulation of PNPs due to the enhanced permeation and retention effect. Micro-LED mediated light irradiation significantly inhibited tumor growth, showcasing remarkable therapeutic efficacy. This integrated approach offers a minimally invasive, highly effective strategy for glioma treatment, combining precise drug targeting with efficient photodynamic therapy, resulting in reduced systemic toxicity and superior therapeutic outcomes.