# Carbon dots penetrating the blood-brain barrier for central nervous system nanomedicine **Authors:** Wubshet Mekonnen Girma, Girum Getachew Demissie, Shewaye Lakew Mekuria, Shamsa Kizhepat, T.M. Subrahmanya, Akash S. Rasal, Binyam Abdu Berhe, Gangaraju Gedda, Yoo-Jin Park, Jia-Yaw Chang, Myung-Geol Pang PMC · DOI: 10.7150/thno.130380 · 2026-02-26 ## TL;DR Carbon dots can cross the blood-brain barrier and offer new ways to diagnose and treat central nervous system diseases. ## Contribution This review introduces carbon dots as a novel nanomedicine platform for CNS diseases by enabling BBB penetration and combined diagnostic and therapeutic functions. ## Key findings - Carbon dots can penetrate the blood-brain barrier through surface modifications. - Carbon dots support multimodal imaging and delivery of therapeutic agents for CNS diseases. - They offer combined diagnostic and therapeutic capabilities for brain disorders and cancers. ## Abstract Central nervous system (CNS) diseases are challenging to treat because of the blood-brain barrier (BBB), formed by tight junctions that limit the transcellular transport of therapeutic drugs. Carbon dots (CDs) have emerged as versatile nanotheranostic platforms for the targeting, diagnosis, and treatment of CNS diseases owing to their ultrasmall size, intrinsic photoluminescence, tunable surface chemistry, and biocompatibility. Surface modifications of CDs with targeting ligands, polymer coatings, biomimetic membranes, and exosome-like molecules enable BBB penetration and selective brain accumulation. CDs also support multimodal imaging techniques, such as fluorescence, magnetic resonance, and photoacoustic imaging, for early disease detection and real-time therapeutic monitoring. In addition, their ability to deliver drugs, genes, and therapeutic agents, combined with their antioxidant, anti-inflammatory, photothermal, photodynamic, and sonodynamic properties, highlights their potential for the integrated diagnosis and treatment of CNS diseases. This review systematically summarizes the background of CDs, the design of BBB-penetrating CDs, and their applications in tumor diagnosis, treatment, and imaging-guided cooperative therapies for CNS diseases. Finally, current obstacles and future perspectives are discussed. This review provides a valuable reference for the rational design of BBB-penetrating CDs for the precise treatment of neurological disorders and brain cancers. ## Full-text entities - **Genes:** Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, SLC7A5 (solute carrier family 7 member 5) [NCBI Gene 8140] {aka 4F2LC, CD98, D16S469E, E16, LAT1, MPE16}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, Ltf (lactotransferrin) [NCBI Gene 17002] {aka Csp82, Lf, MMS10R, Ms10r}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Trem2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 83433] {aka TREM-2, Trem2a, Trem2b, Trem2c}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Ager (advanced glycosylation end product-specific receptor) [NCBI Gene 11596] {aka RAGE}, rab14 (RAB14, member RAS oncogene family) [NCBI Gene 373104] {aka cb731, fc26g11, fj47f07, fj68a01, wu:fc26g11, wu:fj47f07}, Tat (tyrosine aminotransferase) [NCBI Gene 234724], Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, TFRC (transferrin receptor) [NCBI Gene 7037] {aka CD71, IMD46, T9, TFR, TFR1, TR}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Rab14 (RAB14, member RAS oncogene family) [NCBI Gene 68365] {aka 0610030G24Rik, 2810475J17Rik, A830021G03Rik, D030017L14Rik}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, rab13 (RAB13, member RAS oncogene family) [NCBI Gene 373105] {aka cb764, hm:zeh0455}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, LRP1 (LDL receptor related protein 1) [NCBI Gene 4035] {aka A2MR, APOER, APR, CD91, DDH3, IGFBP-3R}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, Vcam1 (vascular cell adhesion molecule 1) [NCBI Gene 22329] {aka CD106, Vcam-1}, lrp1ab (low density lipoprotein receptor-related protein 1Ab) [NCBI Gene 565797] {aka fk86b07, lrp1, lrp1b, si:ch73-60e21.3, wu:fk86b07}, Tfrc (transferrin receptor) [NCBI Gene 22042] {aka 2610028K12Rik, CD71, E430033M20Rik, Mtvr1, TFR, TFR1}, tfa (transferrin-a) [NCBI Gene 30255] {aka cb285, gavi, id:ibd3238, id:ibd3525, sb:cb285, trf}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Rab13 (RAB13, member RAS oncogene family) [NCBI Gene 68328] {aka 0610007N03Rik, B230212B15Rik}, slc2a1a (solute carrier family 2 member 1a) [NCBI Gene 555778] {aka fc29a02, glut1, glut1a, glut1b, slc2a1, wu:fc29a02}, Apoe (apolipoprotein E) [NCBI Gene 11816] {aka Apo-E} - **Diseases:** anxiety (MESH:D001007), schizophrenia (MESH:D012559), neuroinflammation (MESH:D000090862), CNS (MESH:D002493), cytotoxicity (MESH:D064420), traumatic brain injury (MESH:D000070642), lysosomal storage diseases (MESH:D016464), ischemic stroke (MESH:D002544), cancer (MESH:D009369), cerebral ischemia (MESH:D002545), brain glioma (MESH:C564230), infections (MESH:D007239), CD (MESH:D003424), Alzheimer (MESH:D000544), mitochondrial dysfunction (MESH:D028361), intracerebral hemorrhage (MESH:D002543), Parkinson's disease (MESH:D010300), N-CDs (MESH:D007222), brain disease (MESH:D001927), brain injuries (MESH:D001930), U87 glioma tumors (MESH:D005910), epilepsy (MESH:D004827), CNS inflammation (MESH:D007249), disease (MESH:D004194), neurodegeneration (MESH:D019636), Brain cancer (MESH:D001932), CDs (MESH:D000080363), glioblastoma (MESH:D005909), cognitive deficits (MESH:D003072), multiple sclerosis (MESH:D009103), motor deficits (MESH:D009461), AMT (MESH:C567355), stroke (MESH:D020521), amyloid (MESH:C000718787), depression (MESH:D003866), neuronal damage (MESH:D009410) - **Chemicals:** Polymer (MESH:D011108), Alexa Fluor 488 (MESH:C000711379), Se (MESH:D012643), Carbon (MESH:D002244), amine (MESH:D000588), starch (MESH:D013213), Nitrogen (MESH:D009584), temozolomide (MESH:D000077204), PEI (MESH:D011094), PEG (MESH:D011092), carbon nitride (MESH:C011206), carbon nanotubes (MESH:D037742), memantine (MESH:D008559), L-aspartic acid (MESH:D001224), Fucoidan (MESH:C007789), imine (MESH:D007097), Oxygen (MESH:D010100), sulfate (MESH:D013431), phosphorus (MESH:D010758), Gd-DTPA (MESH:D019786), chitosan (MESH:D048271), DOX (MESH:D004317), singlet oxygen (MESH:D026082), zirconium (MESH:D015040), curcumin (MESH:D003474), sulfur (MESH:D013455), EGCG (MESH:C045651), epirubicin (MESH:D015251), N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide (MESH:C569266), porphyrin (MESH:D011166), CD-PEI (-), metal (MESH:D008670), ROS (MESH:D017382), quinine sulphate (MESH:D011803), folic acid (MESH:D005492), CA (MESH:D002118), pentaethylenehexamine (MESH:C031122), Boron (MESH:D001895), hydroxyl radicals (MESH:D017665), NO (MESH:D009569), nitric acid (MESH:D017942), Yb (MESH:D015018), DAPI (MESH:C007293), Manganese (MESH:D008345), D-glucose (MESH:D005947), L-glutamate (MESH:D018698), caffeic acid (MESH:C040048), Cu (MESH:D003300), polydopamine (MESH:C568283), Tween 80 (MESH:D011136), RB (MESH:D012395), NMDA (MESH:D016202), PBS (MESH:D007854), poly(lactic-co-glycolic acid (MESH:D000077182), Agarose (MESH:D012685), OH (MESH:C031356), iron (MESH:D007501), FA (MESH:C004999), lipid (MESH:D008055), water (MESH:D014867) - **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Danio rerio (leopard danio, species) [taxon 7955], Lyssavirus rabies (species) [taxon 11292] - **Mutations:** Q67L - **Cell lines:** N2a — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), RVG29 — Homo sapiens (Human), Amyotrophic lateral sclerosis 1, Induced pluripotent stem cell (CVCL_8999) ## Figures 12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12964387/full.md --- Source: https://tomesphere.com/paper/PMC12964387