# Two-dimensional NIR-II AIE nanotheranostic probes with ultralarge Stokes shifts for surgical navigation and ablation of glioma

**Authors:** Yisheng Liu, Xiang Su, Yong Zhong, Ping Shangguan, Jun Zhu, Zhengqun Luo, Haigang Wu, Dong Wang, Ting Han, Jiefei Wang, Bingyang Shi, Ben Zhong Tang

PMC · DOI: 10.1126/sciadv.aeb5389 · 2026-03-06

## TL;DR

A new two-dimensional NIR-II probe with a large Stokes shift helps in accurately guiding brain tumor surgery and subsequent treatment.

## Contribution

A novel tetracyanoquinodimethane-derived NIR probe (TNQ2) with a 445-nm Stokes shift and aggregation-enhanced emission is developed.

## Key findings

- TNQ2 self-assembles into sub-160 nm two-dimensional J-aggregates with red-shift absorption and aggregation-enhanced emission.
- The probe enables high-sensitivity NIR-II fluorescence imaging-guided glioma resection and phototherapy.
- The strategy establishes a new paradigm for developing advanced NIR phototheranostics for brain diseases.

## Abstract

Near-infrared (NIR) fluorescence probes featuring ultralarge Stokes shifts and efficient aggregate-state luminescence are highly desirable for bioimaging yet remain scarce due to formidable synthetic challenges and intricate photophysical modulation. We report a facile one-step click reaction to synthesize a tetracyanoquinodimethane-derived NIR probe (TNQ2) that overcomes the long-standing nonfluorescence limitation while achieving an unprecedented 445-nanometer Stokes shift. TNQ2 self-assembles into the smallest-sized two-dimensional J-aggregates (sub-160 nanometers) with a red-shift absorption from 545 to 725 nanometers and aggregation-enhanced emission around 1000 nanometers. The radiative/nonradiative modulation balances the fluorescence/photothermal/photodynamic effect to support high-sensitivity NIR-II fluorescence imaging-guided precise glioma resection and postoperative phototherapy to substantially extend survival in orthotopic glioma models. Our molecule/nanoengineering strategy establishes a transformative paradigm for developing advanced NIR phototheranostics for brain diseases.

A 2D NIR-II AIE probe enables precise glioma surgery and postoperative phototherapy via an ultralarge Stokes shift.

## Linked entities

- **Chemicals:** tetracyanoquinodimethane (PubChem CID 73697)
- **Diseases:** glioma (MONDO:0021042)

## Full-text entities

- **Genes:** Dntt (deoxynucleotidyltransferase, terminal) [NCBI Gene 21673] {aka Tdt}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, Gnl3 (guanine nucleotide binding protein nucleolar 3) [NCBI Gene 30877] {aka Ns}, Ang2 (angiogenin, ribonuclease A family, member 2) [NCBI Gene 11731] {aka Angrp, Raa3, Rnase5b}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}
- **Diseases:** Phototoxicity (MESH:D017484), Hemolysis (MESH:D006461), glioma (MESH:D005910), Tumor (MESH:D009369), Glioblastoma (MESH:D005909), brain tumors (MESH:D001932), brain diseases (MESH:D001927), cytotoxicity (MESH:D064420)
- **Chemicals:** CCK-8 (MESH:D012844), water (MESH:D014867), MB (MESH:D008751), MitoSOX Red (MESH:C000597839), DCFH-DA (MESH:C029569), olefins (MESH:D000475), ethanol (MESH:D000431), hydroxyl radical (MESH:D017665), 13C (MESH:C000615229), pyrene (MESH:C030984), metal (MESH:D008670), cyclohexadiene (MESH:C048401), paraffin (MESH:D010232), singlet oxygen (MESH:D026082), NaCl (MESH:D012965), black phosphorus (MESH:D010758), DHE (MESH:C067883), xylene (MESH:D014992), malononitrile (MESH:C000945), streptomycin (MESH:D013307), 2,7-dichlorodihydrofluorescein diacetate (MESH:C110400), C (MESH:D002244), polymer (MESH:D011108), CO2 (MESH:D002245), paraformaldehyde (MESH:C003043), OH (MESH:C031356), THF (MESH:C018674), eosin (MESH:D004801), 4',6-diamidino-2-phenylindole (MESH:C007293), deoxyuridine (MESH:D003857), Mito-SOX (MESH:C521281), alkyne (MESH:D000480), reactive oxygen species (MESH:D017382), 7,7,8,8-tetracyanoquinodimethane (MESH:C013703), Ang-TNQ (-), O2 - (MESH:D013481), Crystal violet (MESH:D005840), H&amp;E (MESH:D006371), Pluronic F127 (MESH:D020442), penicillin (MESH:D010406), hematoxylin (MESH:D006416), Arg-Gly-Asp (MESH:C047981), F127 (MESH:C078661), amino acids (MESH:D000596), Pluronic P123 (MESH:C464484), ICG (MESH:D007208)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** Beas 2B — Homo sapiens (Human), Transformed cell line (CVCL_0168), S25 — Mus musculus (Mouse), Hybridoma (CVCL_G585), HA1800 — Homo sapiens (Human), Transformed cell line (CVCL_1D30), c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103), LO2 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_C7SD), Balb — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0637), U87 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), Balb/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), EC109 — Homo sapiens (Human), Esophageal squamous cell carcinoma, Cancer cell line (CVCL_6898)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965306/full.md

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Source: https://tomesphere.com/paper/PMC12965306