# Organic small-molecule NIR-II fluorophores for tumor phototheranostics

**Authors:** Dan Xiang, Zhichao Wang, Hongwei Zheng, Yuqi Tang, Quan Li

PMC · DOI: 10.1038/s41377-026-02212-w · Light, Science & Applications · 2026-03-16

## TL;DR

This review discusses recent advances in small-molecule NIR-II fluorophores for deep-tissue imaging and cancer therapy, highlighting their potential for clinical use.

## Contribution

The paper provides a systematic summary of molecular engineering strategies and theranostic applications of NIR-II fluorophores over the past five years.

## Key findings

- NIR-II fluorophores enable high-resolution deep-tissue imaging with low phototoxicity.
- Recent developments include efficient photodynamic and photothermal therapeutic modalities using these fluorophores.
- Structure-function relationships and photophysical properties are key to optimizing their performance.

## Abstract

Near-infrared II (NIR-II) fluorophores possess transformative potential for biomedical applications, owing to their deep-tissue penetration, reduced tissue autofluorescence, and low phototoxicity. Recent breakthroughs in molecular engineering have accelerated the development of NIR-II organic small-molecule fluorophores based on versatile scaffolds, including cyanine, boron dipyrromethene, benzobisthiadiazole, xanthene, cyano-based derivatives, and small-molecule metal complexes. This review systematically summarizes the molecular engineering strategies, photophysical properties, and structure-function relationships of NIR-II fluorophores in the last five years. We highlight recent breakthroughs in their theranostic applications, including high-resolution deep-tissue imaging and efficient phototherapeutic modalities such as photodynamic and photothermal therapy. Finally, we present forward-looking perspectives on current challenges and emerging opportunities, aiming to provide insights for promoting continued innovation and clinical translation in this rapidly advancing field.

This review systematically summarizes the recent advances in organic small-molecule NIR-II fluorophores for phototheranostics, providing insights into further innovation and facilitating clinical translation.

## Linked entities

- **Chemicals:** cyanine (PubChem CID 68227), boron dipyrromethene (PubChem CID 25058173), xanthene (PubChem CID 7107)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, Calca (calcitonin/calcitonin-related polypeptide, alpha) [NCBI Gene 12310] {aka CA, CGRP-1, CGRP1, Calc, Calc1, Cgrp}, Slc2a1 (solute carrier family 2 (facilitated glucose transporter), member 1) [NCBI Gene 20525] {aka GT1, Glut-1, Glut1, M100200, Rgsc200}, Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, Oga (O-GlcNAcase) [NCBI Gene 76055] {aka Hy5, Mgea5, Ncoat}, Entpd1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 12495] {aka 2610206B08Rik, ATP-DPH, Cd39, E130009M23Rik, NTPDase-1}, Nt5e (5' nucleotidase, ecto) [NCBI Gene 23959] {aka 2210401F01Rik, 5'-NT, CD73, NT, Nt5, eNT}, Adora2a (adenosine A2a receptor) [NCBI Gene 11540] {aka A2AAR, A2aR, AA2AR, ARA2A}, Hsp84-3 (heat shock protein, 3) [NCBI Gene 104434] {aka 84kDa, Hsp90, hsp3}, Rhd (Rh blood group, D antigen) [NCBI Gene 19746] {aka Rh, Rhced, Rhl1}, Zfp36 (zinc finger protein 36) [NCBI Gene 22695] {aka Gos24, Nup475, TIS11D, TISII, Tis11, Ttp}, Nbas (neuroblastoma amplified sequence) [NCBI Gene 71169] {aka 4933425L03Rik, Nag}, Tst (thiosulfate sulfurtransferase, mitochondrial) [NCBI Gene 22117] {aka rhodanese}, Cga (glycoprotein hormones, alpha subunit) [NCBI Gene 12640] {aka CG-alpha, FSHA, GPHA1, GPHalpha, HCG, LHA}, Trf (transferrin) [NCBI Gene 22041] {aka Cd176, HP, Tf, Tfn, hpx}, Fbrs (fibrosin) [NCBI Gene 14123] {aka Fbs, Fbs1}
- **Diseases:** AKI (MESH:D058186), vascular dysfunction (MESH:D002561), glioma (MESH:D005910), hypoxia (MESH:D000860), GBM (MESH:D005909), PE (MESH:D011655), diabetic nephropathy (MESH:D003928), PCE (MESH:D003291), Cancer (MESH:D009369), Lymphatic metastasis (MESH:D008207), hyperglycemia (MESH:D006943), Breast cancer (MESH:D001943), osteoporosis (MESH:D010024), HT (MESH:D005334), hypoxic (MESH:D002534), hypertension (MESH:D006973), brain tumor (MESH:D001932), necrosis (MESH:D009336), CKD (MESH:D051436), thrombus (MESH:D013927), PTS (MESH:D020521), IBD (MESH:D015212), phototoxicity (MESH:D017484), mercury poisoning (MESH:D008630), infected (MESH:D007239), kidney disease (MESH:D007674), osteoporotic (MESH:D058866), cardiovascular diseases (MESH:D002318), cytotoxicity (MESH:D064420), cervical cancer (MESH:D002583), extrahepatic diseases (MESH:D001651), mitochondrial (MESH:D028361), diabetes (MESH:D003920), venous thromboembolic disease (MESH:D054556), nervous system (MESH:D009422), ischemia (MESH:D007511), colon cancer (MESH:D015179), pancreatic cancer (MESH:D010190)
- **Chemicals:** Ru (MESH:D012428), CH3CN (MESH:C032159), malononitrile (MESH:C000945), aniline (MESH:C023650), singlet oxygen (MESH:D026082), ROS (MESH:D017382), folate (MESH:D005492), hydroxyl radicals (MESH:D017665), NEM (MESH:C058866), thiophene (MESH:D013876), fluoresceins (MESH:D005452), alendronate (MESH:D019386), DMSO (MESH:D004121), DCM (MESH:D008752), H&amp;E (MESH:D006371), H2O2 (MESH:D006861), rhodamine B (MESH:C029773), F127 (MESH:C078661), methylene blue (MESH:D008751), OH (MESH:C031356), EB (MESH:D005070), Si (MESH:D012825), 2,3,5-triphenyltetrazolium chloride (MESH:C009591), GSH (MESH:D005978), Rh (MESH:D012238), Xanthene (MESH:D014966), triazole (MESH:D014230), CPT (MESH:D002166), 99mTc (MESH:D013667), melanin (MESH:D008543), sulfur (MESH:D013455), thiophenol (MESH:C042983), Metal (MESH:D008670), amine (MESH:D000588), N-ethylmaleimide (MESH:D005033), ATP (MESH:D000255), azulene (MESH:C005525), cycloalkene (MESH:D003516), water (MESH:D014867), ADT-OH (MESH:C000712456), P (MESH:D010758), CO (MESH:D002248), DPPC (MESH:D015060), carbazole (MESH:C041514), nitrosamine (MESH:D009602), DSPE-PEG2000 (MESH:C519184), MGO (MESH:D011765), ICG (MESH:D007208), J (MESH:C000608249), nitrogen (MESH:D009584), diphenylamine (MESH:D004159), HCy (MESH:D006710), selenium (MESH:D012643), sorafenib (MESH:D000077157), BTD (MESH:C015700), H2S (MESH:D006862), CAs (MESH:D002118), hydrogen (MESH:D006859), methylene (MESH:C030011), iodine (MESH:D007455)
- **Species:** Escherichia coli (E. coli, species) [taxon 562], Staphylococcus aureus (species) [taxon 1280], Mus musculus (house mouse, species) [taxon 10090], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Escherichia coli Nissle 1917 (strain) [taxon 316435], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), Pan02 — Mus musculus (Mouse), Mouse pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_D627), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), H22 — Homo sapiens (Human), Peripheral primitive neuroectodermal tumor of bone, Cancer cell line (CVCL_1E32), Luc — Homo sapiens (Human), Transformed cell line (CVCL_JY95), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), GL261 — Mus musculus (Mouse), Mouse glioblastoma, Cancer cell line (CVCL_Y003), CT26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), CL4 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_D520)

## Full text

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## Figures

27 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12992625/full.md

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Source: https://tomesphere.com/paper/PMC12992625