JCNRJournal of Clinical and Nursing Research2208-36852208-3693Bio-Byword Scientific Publishing Pty. Ltd.10.26689/jcnr.v8i12.9076ArticleNear-Infrared Light-Responsive Cubic Vesicles for Enhanced Blood-Brain Barrier Permeability and Drug Deliveryhttps://artdesignp.com/journal/JCNR/8/12/10.26689/jcnr.v8i12.9076WangXinyu,ZhengXiaorong,LiJunfei,ShenChangming,ZhangHongyan,JiangJianwei20248122024-12-31Delivering therapeutic agents to the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB). This study presents a novel approach utilizing near-infrared (NIR) light-responsive gold-coated cubic vesicles (Auslip) to modulate BBB permeability and enhance drug delivery to glioma cells. Upon NIR activation, Auslip releases encapsulated agents and transiently opens the BBB. The results demonstrate that Auslip increases doxorubicin (DOX) delivery to glioma C6 cells in a co-culture model with human brain microvascular endothelial cells (hCMEC/D3). This approach offers a promising strategy for CNS therapeutics by enabling simultaneous BBB opening and drug release through optical stimulation.

Ding S, Khan AI, Cai X, et al., 2020, Overcoming blood-brain barrier transport: Advances in nanoparticle-based drug delivery strategies. Mater Today (Kidlington), 37: 112–125. https://doi.org/10.1016/j.mattod.2020.02.001

Pardridge WM, 2005, The blood-brain barrier: bottleneck in brain drug development. NeuroRx, 2(1): 3–14. https://doi.org/10.1602/neurorx.2.1.3

Chen ZA, Wu CH, Wu SH, et al., 2024, Receptor ligand-free mesoporous silica nanoparticles: a streamlined strategy for targeted drug delivery across the blood-brain barrier. ACS Nano, 12716–12736. https://doi.org/10.1021/acsnano.3c08993

Zhao C, Zhu X, Tan J, et al., 2024, Lipid-based nanoparticles to address the limitations of GBM therapy by overcoming the blood-brain barrier, targeting glioblastoma stem cells, and counteracting the immunosuppressive tumor microenvironment. Biomed Pharmacother, 171: 116113. https://doi.org/10.1016/j.biopha.2023.116113

Rapoport SI, 2000, Osmotic Opening of the Blood-Brain Barrier: Principles, Mechanism, and Therapeutic Applications. Cell Mol Neurobiol, 20(2): 217–230. https://doi.org/10.1023/a:1007049806660

Smith-Cohn MA, Burley NB, Grossman SA, 2022, Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking? Curr Neuropharmacol, 20(7): 1383–1399. https://doi.org/10.2174/1570159X20999220131163504

Li T, Bourgeois J-P, Celli S, et al., 2012, Cell-Penetrating Anti-GFAP VHH and Corresponding Fluorescent Fusion Protein VHH-GFP Spontaneously Cross the Blood-Brain Barrier and Specifically Recognize Astrocytes: Application to Brain Imaging. The FASEB Journal, 26(10): 3969–3979. https://doi.org/10.1096/fj.11-201384

Fan CH, Ting CY, Chang YC, et al., 2015, Drug-Loaded Bubbles with Matched Focused Ultrasound Excitation for Concurrent Blood-Brain Barrier Opening and Brain-Tumor Drug Delivery. Acta Biomater, 15: 89–101. https://doi.org/10.1016/j.actbio.2014.12.026

McMahon D, Poon C, Hynynen K, 2019, Evaluating the Safety Profile of Focused Ultrasound and Microbubble-Mediated Treatments to Increase Blood-Brain Barrier Permeability. Expert Opin Drug Deliv, 16(2): 129–142. https://doi.org/10.1080/17425247.2019.1567490

Li X, Vemireddy V, Cai Q, et al., 2021, Reversibly Modulating the Blood-Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles. Nano Lett, 21(22): 9805–9815. https://doi.org/10.1021/acs.nanolett.1c02996

Ash C, Dubec M, Donne K, et al., 2017, Effect of Wavelength and Beam Width on Penetration in Light-Tissue Interaction Using Computational Methods. Lasers Med Sci, 32(8): 1909–1918. https://doi.org/10.1007/s10103-017-2317-4

Li X, Che Z, Mazhar K, et al., 2017, Ultrafast Near-Infrared Light-Triggered Intracellular Uncaging to Probe Cell Signaling. Adv Funct Mater, 27(11): 1605778. https://doi.org/10.1002/adfm.201605778

Wang C, Xie Y, Song X, 2023, A NIR Programmable In Vivo miRNA Magnifier for NIR-II Imaging of Early Stage Cancer. Angew Chem Int Ed Engl, 62(50): e202312665. https://doi.org/10.1002/anie.202312665

Wu D, Chen Q, Chen X, et al., 2023, The Blood-Brain Barrier: Structure, Regulation, and Drug Delivery. Signal Transduct Target Ther, 8(1): 217. https://doi.org/10.1038/s41392-023-01481-w

Li Y, He D, Tu J, et al., 2018, The Comparative Effect of Wrapping Solid Gold Nanoparticles and Hollow Gold Nanoparticles with Doxorubicin-Loaded Thermosensitive Liposomes for Cancer Thermo-Chemotherapy. Nanoscale, 10(18): 8628–8641. https://doi.org/10.1039/C7NR09083H

Neuhaus F, Mueller D, Tanasescu R, et al., 2017, Vesicle Origami: Cuboid Phospholipid Vesicles Formed by Template-Free Self-Assembly. Angew Chem Int Ed Engl, 56(23): 6515–6518. https://doi.org/10.1002/anie.201701634

Anderson JM, Langone JJ, 1999, Issues and Perspectives on the Biocompatibility and Immunotoxicity Evaluation of Implanted Controlled Release Systems. J Control Release, 57(2): 107–113. https://doi.org/10.1016/s0168-3659(98)00178-3

Tagami T, Kubota M, Ozeki T, 2015, Effective Remote Loading of Doxorubicin into DPPC/Poloxamer 188 Hybrid Liposome to Retain Thermosensitive Property and the Assessment of Carrier-Based Acute Cytotoxicity for Pulmonary Administration. J Pharm Sci, 104(11): 3824–3832. https://doi.org/10.1002/jps.24593

Saxena VK, Deb R, Shrivastava S, et al., 2012, Functionalizing Gold Nanoparticles with Bluetongue Virus Multiple Peptide Antigens Utilizing Gold–Thiol Interaction: A Novel Approach to Develop Pen Side Test. Res Vet Sci, 93(3): 1531–1536. https://doi.org/10.1016/j.rvsc.2012.04.013

Galanzha EI, Nedosekin DA, Sarimollaoglu M, et al., 2013, Photoacoustic and Photothermal Cytometry Using Photoswitchable Proteins and Nanoparticles with Ultrasharp Resonances. J Biophotonics, 8(1–2): 81–93. https://doi.org/10.1002/jbio.201300140. Erratum in J Biophotonics, 8(8): 687. https://doi.org/10.1002/jbio.201580140

Qiao L, Qin Y, Wang Y, et al., 2020, A Brain Glioma Gene Delivery Strategy by Angiopep-2 and TAT-Modified Magnetic Lipid-Polymer Hybrid Nanoparticles. RSC Advances, 10(68): 41471–41481. https://doi.org/10.1039/D0RA07161G

Weissleder R, 2001, A Clearer Vision for In Vivo Imaging. Nat Biotechnol, 19(4): 316–317. https://doi.org/10.1038/86684

Cherkasov VR, Mochalova EN, Babenyshev AV, et al., 2020, Antibody-Directed Metal-Organic Framework Nanoparticles for Targeted Drug Delivery. Acta Biomater, 103: 223–236. https://doi.org/10.1016/j.actbio.2019.12.012