International Journal of Nanomedicine (Mar 2024)
Nanoparticle-Based Combinational Strategies for Overcoming the Blood-Brain Barrier and Blood-Tumor Barrier
Abstract
Su Hyun Lim,1,2 Gi Taek Yee,3 Dongwoo Khang1,2,4 1Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, South Korea; 2Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, South Korea; 3Department of Neurosurgery, Gil Medical Center, Gachon University, School of Medicine, Incheon, 21565, South Korea; 4Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, South KoreaCorrespondence: Dongwoo Khang, Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, South Korea, Tel +82 32 899 1525, Email [email protected] Gi Taek Yee, Department of Neurosurgery, College of Medicine, Gil Medical Center, Gachon University, Incheon, 21565, South Korea, Tel +82-32-460-3304, Email [email protected]: The blood-brain barrier (BBB) and blood-tumor barrier (BTB) pose substantial challenges to efficacious drug delivery for glioblastoma multiforme (GBM), a primary brain tumor with poor prognosis. Nanoparticle-based combinational strategies have emerged as promising modalities to overcome these barriers and enhance drug penetration into the brain parenchyma. This review discusses various nanoparticle-based combinatorial approaches that combine nanoparticles with cell-based drug delivery, viral drug delivery, focused ultrasound, magnetic field, and intranasal drug delivery to enhance drug permeability across the BBB and BTB. Cell-based drug delivery involves using engineered cells as carriers for nanoparticles, taking advantage of their intrinsic migratory and homing capabilities to facilitate the transport of therapeutic payloads across BBB and BTB. Viral drug delivery uses engineered viral vectors to deliver therapeutic genes or payloads to specific cells within the GBM microenvironment. Focused ultrasound, coupled with microbubbles or nanoparticles, can temporarily disrupt the BBB to increase drug permeability. Magnetic field-guided drug delivery exploits magnetic nanoparticles to facilitate targeted drug delivery under an external magnetic field. Intranasal drug delivery offers a minimally invasive avenue to bypass the BBB and deliver therapeutic agents directly to the brain via olfactory and trigeminal pathways. By combining these strategies, synergistic effects can enhance drug delivery efficiency, improve therapeutic efficacy, and reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination strategies, and advancing preclinical and clinical investigations to promote the translation of nanoparticle-based combination therapies for GBM. Keywords: glioblastoma, blood-brain barrier, blood-tumor barrier, nanoparticle, combination strategy, ultrasound-wave, magnetic field, intranasal drug delivery
