NIR-II cyanine@albumin fluorophore for deep tissue imaging and imaging-guided surgery

Abstract

The near-infrared (NIR)-II bioimaging technique is highly important for both diagnosing and treating life-threatening diseases due to its exceptional imaging capabilities. However, the lack of suitable NIR-II fluorescent probes has hindered their widespread clinical application. To address this issue, the binding of albumin to cyanine dyes has emerged as a practical and efficient method for developing high-performance NIR-II probes. Cyanine dyes can bind with exogenous and endogenous albumin through either covalent or noncovalent interactions, serving various purposes. The resulting cyanine@albumin (or albumin@cyanine) fluorophores offer significant advantages, including strong brightness, excellent photostability, good biosafety, and a long-term, high-resolution imaging window. Cyanine dye in situ binding with endogenous albumin can also enhance the targeting imaging capability. This review provides a summary of the interaction mechanism, performance enhancement, tumor-targeting feature, and in vivo imaging applications of the cyanine@albumin fluorophores. These advancements not only highlight the unique characteristics of cyanine@albumin fluorophores in preclinical research but also emphasize their potential for clinical diagnosis.

Keywords

cancer detection / covalent binding / cyanine dye / cyanine@albumin / NIR-II imaging-guided surgery

References

[1] Tang Y, Pei F, Lu X, Fan Q, Huang W. Recent advances on activatable NIR-II fluorescence probes for biomedical imaging. Adv Opt Mater. 2019; 7(21): 1900917.

[2] Zhu S, Tian R, Antaris AL, Chen X, Dai H. Near-infrared-II molecular dyes for cancer imaging and surgery. Adv Mater. 2019; 31(24): 1900321.

[3] Li L, Dong X, Li J, Wei J. A short review on NIR-II organic small molecule dyes. Dyes Pigm. 2020; 183: 108756.

[4] Han T, Wang Y, Xu J, et al. Surfactant-chaperoned donor–acceptor–donor NIR-II dye strategy efficiently circumvents intermolecular aggregation to afford enhanced bioimaging contrast. Chem Sci. 2022; 13(44): 13201-13211.

[5] Han T, Wang Y, Ma S, et al. Near-infrared carbonized polymer dots for NIR-II bioimaging. Adv Sci. 2022; 9(30): 2203474.

[6] Li M, Zheng X, Han T, et al. Near-infrared-II ratiometric fluorescence probes for non-invasive detection and precise navigation surgery of metastatic sentinel lymph nodes. Theranostics. 2022; 12(16): 7191-7202.

[7] Li C, Guan X, Zhang X, et al. NIR-II bioimaging of small molecule fluorophores: from basic research to clinical applications. Biosens Bioelectron. 2022; 216: 114620.

[8] Wang Y, Nan J, Ma H, et al. NIR-II imaging and sandwiched plasmonic biosensor for ultrasensitive intraoperative definition of tumor-invaded lymph nodes. Nano Lett. 2023; 23(9): 4039-4048.

[9] Tian R, Ma H, Yang Q, et al. Rational design of a super-contrast NIR-II fluorophore affords high-performance NIR-II molecular imaging guided microsurgery. Chem Sci. 2019; 10(1): 326-332.

[10] Ren TB, Wang ZY, Xiang Z, et al. A general strategy for development of activatable NIR-II fluorescent probes for in vivo high-contrast bioimaging. Angew Chem Int Ed. 2021; 60(2): 800-805.

[11] Lei Z, Zhang F. Molecular engineering of NIR-II fluorophores for improved biomedical detection. Angew Chem Int Ed. 2021; 60(30): 16294-16308.

[12] Su Y, Yu B, Wang S, Cong H, Shen Y. NIR-II bioimaging of small organic molecule. Biomaterials. 2021; 271: 120717.

[13] Wang Y, Yang T, Ke H, et al. Smart albumin-biomineralized nanocomposites for multimodal imaging and photothermal tumor ablation. Adv Mater. 2015; 27(26): 3874-3882.

[14] Liu Z, Chen X. Simple bioconjugate chemistry serves great clinical advances: albumin as a versatile platform for diagnosis and precision therapy. Chem Soc Rev. 2016; 45(5): 1432-1456.

[15] Hoogenboezem EN, Duvall CL. Harnessing albumin as a carrier for cancer therapies. Adv Drug Deliv Rev. 2018; 130: 73-89.

[16] Antaris AL, Chen H, Diao S, et al. A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. Nat Commun. 2017; 8(1): 15269.

[17] Zeng X, Xiao Y, Lin J, et al. Near-infrared II dye-protein complex for biomedical imaging and imaging-guided photothermal therapy. Adv Healthcare Mater. 2018; 7(18): 1800589.

[18] Raabe A, Beck J, Gerlach R, Zimmermann M, Seifert V. Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow. Neurosurgery. 2003; 52(1): 132-139.

[19] Vinegoni C, Botnaru I, Aikawa E, et al. Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques. Sci Transl Med. 2011; 3(84): 84ra45.

[20] Zhu S, Yung BC, Chandra S, Niu G, Antaris AL, Chen X. Near-infrared-II (NIR-II) bioimaging via off-peak NIR-I fluorescence emission. Theranostics. 2018; 8(15): 4141-4151.

[21] Hong G, Antaris AL, Dai H. Near-infrared fluorophores for biomedical imaging. Nat Biomed Eng. 2017; 1(1): 0010.

[22] Wu D, Chen L, Lee W, Ko G, Yin J, Yoon J. Recent progress in the development of organic dye based near-infrared fluorescence probes for metal ions. Coord Chem Rev. 2018; 354: 74-97.

[23] Chen Y, Li L, Chen W, Chen H, Yin J. Near-infrared small molecular fluorescent dyes for photothermal therapy. Chin Chem Lett. 2019; 30(7): 1353-1360.

[24] Li Y, Zhou Y, Yue X, Dai Z. Cyanine conjugate-based biomedical imaging probes. Adv Healthcare Mater. 2020; 9(22): e2001327.

[25] Du Y, Liu X, Zhu S. Near-infrared-II cyanine/polymethine dyes, current state and perspective. Front Chem. 2021; 9: 718709.

[26] Li DH, Gamage RS, Smith BD. Sterically shielded hydrophilic analogs of indocyanine green. J Org Chem. 2022; 87(17): 11593-11601.

[27] Cosco ED, Caram JR, Bruns OT, et al. Flavylium polymethine fluorophores for near-and shortwave infrared imaging. Angew Chem Int Ed. 2017; 56(42): 13126-13129.

[28] Swamy MMM, Murai Y, Monde K, Tsuboi S, Jin T. Shortwave-infrared fluorescent molecular imaging probes based on π-conjugation extended indocyanine green. Bioconjug Chem. 2021; 32(8): 1541-1547.

[29] Lei Z, Sun C, Pei P, et al. Stable, wavelength-tunable fluorescen. dyes in the NIR-II region for in vivo high-contrast bioimaging and multiplexed biosensing. Angew Chem Int Ed. 2019; 58(24): 8166-8171.

[30] Bandi VG, Luciano MP, Saccomano M, et al. Targeted multicolor in vivo imaging over 1, 000 nm enabled by nonamethine cyanines. Nature Methods. 2022; 19(3): 353-358.

[31] Liu MH, Zhang Z, Yang YC, Chan YH. Polymethine-based semiconducting polymer dots with narrow-band emission and absorption/emission maxima at NIR-II for bioimaging. Angew Chem Int Ed. 2021; 60(2): 983-989.

[32] Shi Y, Yuan W, Liu Q, et al. Development of polyene-bridged hybrid rhodamine fluorophores for high-resolution NIR-II imaging. ACS Mater Lett. 2019; 1(4): 418-424.

[33] Dou K, Feng W, Fan C, Cao Y, Xiang Y, Liu Z. Flexible designing strategy to construct activatable NIR-II fluorescent probes with emission maxima beyond 1200 nm. Anal Chem. 2021; 93(8): 4006-4014.

[34] Chen W, Cheng CA, Cosco ED, et al. Shortwave infrared imaging with J-aggregates stabilized in hollow mesoporous silica nanoparticles. J Am Chem Soc. 2019; 141(32): 12475-12480.

[35] Azhdarinia A, Wilganowski N, Robinson H, et al. Characterization of chemical, radiochemical and optical properties of a dual-labeled MMP-9 targeting peptide. Bioorg Med Chem. 2011; 19(12): 3769-3776.

[36] Zhu S, Hu Z, Tian R, et al. Repurposing cyanine NIR-I dyes accelerates clinical translation of near-infrared-II (NIR-II) bioimaging. Adv Mater. 2018; 30(34): 1802546.

[37] Jin T, Tsuboi S, Komatsuzaki A, et al. Enhancement of aqueous stability and fluorescence brightness of indocyanine green using small calix[4]arene micelles for near-infrared fluorescence imaging. Med Chem Comm. 2016; 7(4): 623-631.

[38] Gorka AP, Nani RR, Schnermann MJ. Harnessing cyanine reactivity for optical imaging and drug delivery. Acc Chem Res. 2018; 51(12): 3226-3235.

[39] Usama SM, Thavornpradit S, Burgess K. Optimized heptamethine cyanines for photodynamic therapy. ACS Appl Bio Mater. 2018; 1(4): 1195-1205.

[40] Ding B, Xiao Y, Zhou H, et al. Polymethine thiopyrylium fluorophores with absorption beyond 1000 nm for biological imaging in the second near-infrared subwindow. J Med Chem. 2019; 62(4): 2049-2059.

[41] Feng L, Chen W, Ma X, Liu SH, Yin J. Near-infrared heptamethine cyanines (Cy7): from structure, property to application. Org Biomol Chem. 2020; 18(46): 9385-9397.

[42] Exner RM, Cortezon-Tamarit F. Pascu SI. Explorations into the effect of meso-substituents in tricarbocyanine dyes: a path to diverse biomolecular probes and materials. Angew Chem Int Ed. 2021; 60(12): 6230-6241.

[43] Sun C, Li B, Zhao M, et al. J-aggregates of cyanine dye for NIR-II in vivo dynamic vascular imaging beyond 1500 nm. J Am Chem Soc. 2019; 141(49): 19221-19225.

[44] Tao Z, Hong G, Shinji C, et al. Biological imaging using nanoparticles of small organic molecules with fluorescence emission at wavelengths longer than 1000 nm. Angew Chem Int Ed. 2013; 52(49): 13002-13006.

[45] Cosco ED, Spearman AL, Ramakrishnan S, et al. Shortwave infrared polymethine fluorophores matched to excitation lasers enable non-invasive, multicolour in vivo imaging in real time. Nat Chem. 2020; 12(12): 1123-1130.

[46] Semonin OE, Johnson JC, Luther JM, Midgett AG, Nozik AJ, Beard MC. Absolute photoluminescence quantum yields of IR-26 dye, PbS, and PbSe quantum dots. J Phys Chem Lett. 2010; 1(16): 2445-2450.

[47] Cosco ED, Arús BA, Spearman AL, et al. Bright chromenylium polymethine dyes enable fast, four-color i. vivo imaging with shortwave infrared detection. J Am Chem Soc. 2021; 143(18): 6836-6846.

[48] Zeng Z, Liew SS, Wei X, Pu K. Hemicyanine-based near-infrared activatable probes for imaging and diagnosis of diseases. Angew Chem Int Ed. 2021; 60(51): 26454-26475.

[49] Li K, Duan X, Jiang Z, et al. J-aggregates of meso-[2.2]paracyclophanyl-BODIPY dye for NIR-II imaging. Nat Commun. 2021; 12(1): 2376.

[50] Li B, Lu L, Zhao M, Lei Z, Zhang F. An efficient 1064 nm NIR-II excitation fluorescent molecular dye for deep-tissue high-resolution dynamic bioimaging. Angew Chem Int Ed. 2018; 57(25): 7483-7487.

[51] Hwang H, Myong S. Protein induced fluorescence enhancement (PIFE) for probing protein-nucleic acid interactions. Chem Soc Rev. 2014; 43(4): 1221-1229.

[52] Bunschoten A, Buckle T, Kuil J, et al. Targeted non-covalent self-assembled nanoparticles based on human serum albumin. Biomaterials. 2012; 33(3): 867-875.

[53] Carr JA, Franke D, Caram JR, et al. Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green. Proc Natl Acad Sci. 2018; 115(17): 4465-4470.

[54] Cai Z, Zhu L, Wang M, Roe AW, Xi W, Qian J. NIR-II fluorescence microscopic imaging of cortical vasculature in non-human primates. Theranostics. 2020; 10(9): 4265-4276.

[55] Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol. 2014; 61(2): 396-407.

[56] Sheng Z, Hu D, Zheng M, et al. Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy. ACS Nano. 2014; 8(12): 12310-12322.

[57] Zhou B, Li Y, Niu G, Lan M, Jia Q, Liang Q. Near-infrared organic dye-based nanoagent for the photothermal therapy of cancer. ACS Appl Mater Interfaces. 2016; 8(44): 29899-29905.

[58] Gao S, Wei G, Zhang S, et al. Albumin tailoring fluorescence and photothermal conversion effect of near-infrared-II fluorophore with aggregation-induced emission characteristics. Nat Commun. 2019; 10(1): 2206.

[59] Li D, Qu C, Liu Q, et al. Monitoring the real-time circulatory system-related physiological and pathological processes in vivo using a multifunctional NIR-II probe. Adv Funct Mater. 2020; 30(6): 1906343.

[60] Chiu TW, Peng CJ, Chen MC, et al. Constructing conjugate vaccine against salmonella typhimurium using lipid-a free lipopolysaccharide. J Biomed Sci. 2020; 27(1): 89.

[61] Williams RJ, Lipowska M, Patonay G, Strekowski L. Comparison of covalent and noncovalent labeling with near-infrared dyes for the high-performance liquid chromatographic determination of human serum albumin. Anal Chem. 1993; 65(5): 601-605.

[62] Berezin MY, Lee H, Akers W, Nikiforovich G, Achilefu S. Ratiometric analysis of fluorescence lifetime for probing binding sites in albumin with near-infrared fluorescent molecular probes. Photochem Photobiol. 2007; 83(6): 1371-1378.

[63] Cohen S, Margel S. Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer. J Nanobiotechnology. 2012; 10: 36.

[64] Wang W, Huang Y, Zhao S, Shao T, Cheng Y. Human serum albumin (HSA) nanoparticles stabilized with intermolecular disulfide bonds. Chem Commun. 2013; 49(22): 2234-2236.

[65] He M, Wu D, Zhang Y, et al. Protein-enhanced NIR-IIb emission of indocyanine Green for functional bioimaging. ACS Appl Bio Mater. 2020; 3(12): 9126-9134.

[66] Xu P, Hu L, Yu C, et al. Unsymmetrical cyanine dye via in vivo hitchhiking endogenous albumin affords high-performance NIR-II/photoacoustic imaging and photothermal therapy. J Nanobiotechnology. 2021; 19(1): 334.

[67] Rong P, Huang P, Liu Z, et al. Protein-based photothermal theranostics for imaging-guided cancer therapy. Nanoscale. 2015; 7(39): 16330-16336.

[68] Bai L, Hu Z, Han T, et al. Super-stable cyanine@albumin fluorophore for enhanced NIR-II bioimaging. Theranostics. 2022; 12(10): 4536-4547.

[69] Xu J, Du Y, Han T, Zhu N, Zhu S. Protein@cyanine-based NIR-II lymphography enables the supersensitive visualization of lymphedema and tumor lymphatic metastasis. Adv Healthc Mater. 2023; 12: 2301051.

[70] Zhang F, Xu J, Yue Y, et al. Three-dimensional histological electrophoresis enables fast automatic distinguishment of cancer margins and lymph node metastases. Sci Adv. 2023; 9(26): eadg2690.

[71] Tian R, Zeng Q, Zhu S, et al. Albumin-chaperoned cyanine dye yields superbright NIR-II fluorophore with enhanced pharmacokinetics. Sci Adv. 2019; 5(9): eaaw0672.

[72] Tian R, Feng X, Wei L, et al. A genetic engineering strategy for editing near-infrared-II fluorophores. Nat Commun. 2022; 13(1): 2853.

[73] Feng Z, Yu X, Jiang M, et al. Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor. Theranostics. 2019; 9(19): 5706-5719.

[74] Du B, Qu C, Qian K, et al. An IR820 dye–protein complex for second near-infrared window and photoacoustic imaging. Adv Opt Mater. 2020; 8(4): 1901471.

[75] Chen, Q, Wang C, Zhan Z, et al. Near-infrared dye bound albumin with separated imaging and therapy wavelength channels for imaging-guided photothermal therapy. Biomaterials. 2014; 35(28): 8206-8214.

[76] Usama SM, Park GK, Nomura S, Baek Y, Choi HS, Burgess K. Role of albumin in accumulation and persistence of tumor-seeking cyanine dyes. Bioconjug Chem. 2020; 31(2): 248-259.

[77] Xu Y, Yang C, Wu Y, et al. In situ albumin-hitchhiking NIR-II probes for accurate detection of micrometastases. Nano Lett. 2023; 23(12): 5731-5737.

[78] Vantourout JC, Mason AM, Yuen J, et al. In vivo half-life extension of BMP1/TLL metalloproteinase inhibitors using small-molecule human serum albumin binders. Bioconjug Chem. 2021; 32(2): 279-289.

[79] Höltke C, Grewer M, Stölting M, Geyer C, Wildgruber M, Helfen A. Exploring the influence of different albumin binders on molecular imaging probe distribution. Mol Pharmaceutics. 2021; 18(7): 2574-2585.

[80] Höltke C, Alsibai W, Grewer M, et al. How different albumin-binders drive probe distribution of fluorescent RGD mimetics. Front Chem. 2021; 9: 689850.

[81] Lemdani K, Salmon H, Gahoual R, et al. Assessment of the targeting specificity of a fluorescent albumin conceived as a preclinical agent of the liver function. Nanoscale. 2018; 10(45): 21151-21160.

[82] Strekowski L, Lipowska M, Patonay G. Substitution reactions of a nucleofugal group in heptamethine cyanine dyes. Synthesis of an isothiocyanato derivative for labeling of proteins with a near-infrared chromophore. J Org Chem. 1992; 57(17): 4578-4580.

[83] Usama SM, Lin C-M, Burgess K. On the mechanisms of uptake of tumor-seeking cyanine dyes. Bioconjug Chem. 2018; 29(11): 3886-3895.

[84] Lin CM, Usama S, Burgess K. Site-specific labeling of proteins with near-IR heptamethine cyanine dyes. Molecules. 2018; 23(11): 2900.

[85] Canovas C, Bellaye PS, Moreau M, Romieu A, Denat F, Goncalves V. Site-specific near-infrared fluorescent labelling of proteins on cysteine residues with meso-chloro-substituted heptamethine cyanine dyes. Org Biomol Chem. 2018; 16(45): 8831-8836.

[86] Xing P, Niu Y, Mu R, et al. A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo. Nat Commun. 2020; 11(1): 1573.

[87] Tian R, Ma H, Zhu S, et al. In vivo imaging: multiplexed NIR-II probes for lymph node-invaded cancer detection and imaging-guided surgery. Adv Mater. 2020; 32(11): 2070086.

[88] Awasthi K, Nishimura G. Modification of near-infrared cyanine dyes by serum albumin protein. Photochem Photobiol Sci. 2011; 10(4): 461-463.

[89] Chen Q, Liang C, Wang C, Liu Z. An imagable and photothermal “abraxane-like” nanodrug for combination cancer therapy to treat subcutaneous and metastatic breast tumors. Adv Mater. 2015; 27(5): 903-910.

[90] Bhavane R, Starosolski Z, Stupin I, Ghaghada KB, Annapragada A. NIR-II fluorescence imaging using indocyanine green nanoparticles. Sci Rep. 2018; 8(1): 14455.

[91] Ganson NJ, Povsic TJ, Sullenger BA, et al. Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer. J Allergy Clin Immunol. 2016; 137(5): 1610-1613.e7.

[92] Feng X, Cao Y, Zhuang P, et al. Rational synthesis of IR820–albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction. RSC Adv. 2022; 12(19): 12136-12144.

[93] Usama SM, Burgess K. Hows and whys of tumor-seeking dyes. Acc Chem Res. 2021; 54(9): 2121-2131.

[94] Vlek SL, van Dam DA, Rubinstein SM, et al. Biliary tract visualization using near-infrared imaging with indocyanine green during laparoscopic cholecystectomy: results of a systematic review. Surg Endosc. 2017; 31(7): 2731-2742.

[95] Vahrmeijer AL, Hutteman M, van der Vorst JR, van de Velde CJH, Frangioni JV. Image-guided cancer surgery using near-infrared fluorescence. Nat Rev Clin Oncol. 2013; 10(9): 507-518.

[96] Chi C, Du Y, Ye J, et al. Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology. Theranostics. 2014; 4(11): 1072-1084.

[97] Demarchi MS, Seeliger B, Lifante JC, Alesina PF, Triponez F. Fluorescence image-guided surgery for thyroid cancer: utility for preventing hypoparathyroidism. Cancers. 2021; 13(15): 3792.

[98] Xu J, Han T, Wang Y, et al. Ultrabright renal-clearable cyanine-protein nanoprobes for high-quality NIR-II angiography and lymphography. Nano Lett. 2022; 22(19): 7965-7975.

[99] Tang X, Ren J, Wei X, et al. Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch. Nat Commun. 2023; 14(1): 2417.

[100] Choi PJ, Park TH, Cooper E, Dragunow M, Denny WA, Jose J. Heptamethine cyanine dye mediated drug delivery: hype or hope. Bioconjug Chem. 2020; 31(7): 1724-1739.

[101] Hou SS, Yang J, Lee JH, et al. Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice. Nat Biomed Eng. 2023; 7: 270-280.

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