Application of nanoprobe based on aggregation-induced luminescence in photothermal diagnosis and treatment of prostate cancer

doi:10.12307/2025.425

Abstract

Abstract:

BACKGROUND: A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers, tumor diagnosis, and bacterial imaging recognition.

OBJECTIVE: To prepare a near-infrared II nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence, and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.

METHODS: Lecithin, polyethylene glycol phospholipids, folate polyethylene glycol phospholipids, and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials. The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method, and basic characterization of the nanoprobe was detected. PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects. The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected. PC3 human prostate cancer cells were selected as the experimental objects. Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy. PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model, and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein. The mice were immediately subjected to near-infraced II fluorescence imaging. 12 hours later, the tumor was irradiated by laser for 5 minutes, and the photothermal treatment effect was observed within 14 days.
RESULTS AND CONCLUSION: (1) The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of (171.0±0.3) nm showed a well-defined spherical morphology. The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared II which emitted a bright near-infrared II fluorescence signal under laser irradiation. (2) The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity. The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells. (3) The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared II fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours. The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm. The tumor volume of mice was significantly smaller after 14 days of treatment. (4) The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared II fluorescence imaging and photothermal therapy of prostate cancer effectively, which may provide a new method for early diagnosis and combined treatment of prostate cancer.

Key words: prostate cancer, aggregation-induced emission, nanoprobe, near-infrared II fluorescence imaging, photothermal therapy, theranostic

CLC Number:

Gui Bin, Jiang Nan, Huang Xin, Zhong Fanglu, Wang Zhiwen, Liu Qianhui, Guo Yuxin, Chen Yueying, Pu Huan, Deng Qing. Application of nanoprobe based on aggregation-induced luminescence in photothermal diagnosis and treatment of prostate cancer[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(16): 3400-3409.

Figures/Tables 7

References

[1] SUNG H, FERLAY J, SIEGEL RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249.
[2] 赫捷,陈万青,李霓,等.中国前列腺癌筛查与早诊早治指南(2022,北京)[J].中华肿瘤杂志,2022,44(1):29-53.
[3] FENG RM, ZONG YN, CAO SM, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond). 2019;39(1):22.
[4] 吴炯,胡嘉华,施美芳,等.前列腺癌生物标志物研究进展[J].检验医学,2023,38(2):190-195.
[5] MOTTET N, VAN DEN BERGH RCN, BRIERS E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021;79(2):243-262.
[6] 孟小丽,康飞,全志永,等.多参数MRI联合68Ga-PSMA PET/CT诊断临床显著性前列腺癌[J].中华核医学与分子影像杂志,2024,44(1): 25-29.
[7] 岳丽娜,贺雅萍,樊佳,等.多参数磁共振成像技术诊断PCa研究进展[J].医学影像学杂志,2024,34(2):128-131.
[8] HEESAKKERS J, FARAG F, BAUER RM, et al. Pathophysiology and Contributing Factors in Postprostatectomy Incontinence: A Review. Eur Urol. 2017;71(6):936-944.
[9] LEI Z, ZHANG F. Molecular Engineering of NIR-II Fluorophores for Improved Biomedical Detection. Angew Chem Int Ed Engl. 2021;60(30): 16294-16308.
[10] LI B, ZHAO M, FENG L, et al. Organic NIR-II molecule with long blood half-life for in vivo dynamic vascular imaging. Nat Commun. 2020;11(1): 3102.
[11] MEI J, HUANG Y, TIAN H . Progress and Trends in AIE-Based Bioprobes: A Brief Overview. ACS Appl Mater Interfaces. 2018;10(15):12217-12261.
[12] LUO J, XIE Z, LAM JW, et al. Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chem Commun (Camb). 2001;(18):1740-1741.
[13] HONG Y, LAM JW, TANG BZ. Aggregation-induced emission: phenomenon, mechanism and applications. Chem Commun (Camb). 2009;(29):4332-4353.
[14] MEI J, LEUNG NL, KWOK RT, et al. Aggregation-Induced Emission: Together We Shine, United We Soar! Chem Rev. 2015;115(21): 11718-11940.
[15] LIN X, LI W, WEN Y, et al. Aggregation-induced emission (AIE)-Based nanocomposites for intracellular biological process monitoring and photodynamic therapy. Biomaterials. 2022;287:121603.
[16] LI Y, HE D, ZHENG Q, et al. Single-Component Photochemical Afterglow Near-Infrared Luminescent Nano-Photosensitizers: Bioimaging and Photodynamic Therapy. Adv Healthc Mater. 2024:13(13):e2304392.
[17] HE X, YU J, YIN R, et al. An AIEgen and Iodine Double-Ornamented Platinum(II) Complex for Bimodal Imaging-Guided Chemo-Photodynamic Combination Therapy. Small. 2024;20(23):e2309894.
[18] 何玉芳,唐文洁,江新青.具有聚集诱导发光特性的纳米材料在肿瘤诊断和治疗中的研究进展[J].中华核医学与分子影像杂志, 2020,40(6):373-377.
[19] SONG S, ZHAO Y, KANG M, et al. An NIR-II Excitable AIE Small Molecule with Multimodal Phototheranostic Features for Orthotopic Breast Cancer Treatment. Adv Mater. 2024;36(14):e2309748.
[20] CUI M, TANG D, WANG B, et al. Bioorthogonal Guided Activation of cGAS-STING by AIE Photosensitizer Nanoparticles for Targeted Tumor Therapy and Imaging. Adv Mater. 2023;35(52):e2305668.
[21] LIU S, LI Y, KWOK RTK, et al. Structural and process controls of AIEgens for NIR-II theranostics. Chem Sci. 2020;12(10):3427-3436.
[22] LI Y, CAI Z, LIU S, et al. Design of AIEgens for near-infrared IIb imaging through structural modulation at molecular and morphological levels. Nat Commun. 2020;11(1):1255.
[23] CUI S, FAN S, TAN H, et al. Ultra-homogeneous NIR-II fluorescent self-assembled nanoprobe with AIE properties for photothermal therapy of prostate cancer. Nanoscale. 2021;13(37):15569-15575.
[24] 李文兰,王文渊,任文秀,等.制备近红外光响应性仿生纳米探针及在乳腺癌光热诊疗中的应用[J]. 中国组织工程研究,2024,28(5): 669-675.
[25] GENG B, HU J, LI Y, et al. Near-infrared phosphorescent carbon dots for sonodynamic precision tumor therapy. Nat Commun. 2022;13(1):5735.
[26] LIANG S, HU D, LI G, et al. NIR-II fluorescence visualization of ultrasound-induced blood-brain barrier opening for enhanced photothermal therapy against glioblastoma using indocyanine green microbubbles. Sci Bull (Beijing). 2022;67(22):2316-2326.
[27] HU Z, FANG C, LI B, et al. First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows. Nat Biomed Eng. 2020;4(3):259-271.
[28] WU GL, LIU F, LI N, et al. Tumor Microenvironment-Responsive One-for-All Molecular-Engineered Nanoplatform Enables NIR-II Fluorescence Imaging-Guided Combinational Cancer Therapy. Anal Chem. 2023; 95(47):17372-17383.
[29] WANG Y, FENG M, LIN B, et al. MET-targeted NIR II luminescence diagnosis and up-conversion guided photodynamic therapy for triple-negative breast cancer based on a lanthanide nanoprobe. Nanoscale. 2021;13(43):18125-18133.
[30] XIE Q, LIU J, CHEN B, et al. NIR-II Fluorescent Activatable Drug Delivery Nanoplatform for Cancer-Targeted Combined Photodynamic and Chemotherapy. ACS Appl Bio Mater. 2022;5(2):711-722.
[31] MOURATIDIS PX, RIVENS I, TER HAAR G. A study of thermal dose-induced autophagy, apoptosis and necroptosis in colon cancer cells. Int J Hyperthermia. 2015;31(5):476-488.
[32] SPYRATOU E, MAKROPOULOU M, EFSTATHOPOULOS EP, et al. Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles. Cancers (Basel). 2017;9(12):173.
[33] ASSARAF YG, LEAMON C, PREDDY JA. The folate receptor as a rational therapeutic target for personalized cancer treatment. Drug Resist Updat. 2014;17(4-6):89-95.
[34] MANDAL AK, WU X, FERREIRA JS, et al. Fluorescent sp(3) Defect-Tailored Carbon Nanotubes Enable NIR-II Single Particle Imaging in Live Brain Slices at Ultra-Low Excitation Doses. Sci Rep. 2020;10(1):5286.
[35] DAHAL D, RAY P, PAN D. Unlocking the power of optical imaging in the second biological window: Structuring near-infrared II materials from organic molecules to nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021;13(6):e1734.
[36] LI B, WANG G, TONG Y, et al. Noninvasive Gastrointestinal Tract Imaging Using BSA-Ag(2)Te Quantum Dots as a CT/NIR-II Fluorescence Dual-Modal Imaging Probe in Vivo. ACS Biomater Sci Eng. 2023;9(1):449-457.
[37] CHEN HJ, QIN Y, WANG ZG, et al. An Activatable and Reversible Virus-Mimicking NIR-II Nanoprobe for Monitoring the Progression of Viral Encephalitis. Angew Chem Int Ed Engl. 2022;61(39):e202210285.
[38] CHEN LL, ZHAO L, WANG ZG, et al. Near-Infrared-II Quantum Dots for In Vivo Imaging and Cancer Therapy. Small. 2022;18(8):e2104567.
[39] ZHANG X, HE S, DING B, et al. Synergistic strategy of rare-earth doped nanoparticles for NIR-II biomedical imaging. J Mater Chem B. 2021;9(44):9116-9122.
[40] WEI Z, DUAN G, HUANG B, et al. Rapidly liver-clearable rare-earth core-shell nanoprobe for dual-modal breast cancer imaging in the second near-infrared window. J Nanobiotechnology. 2021;19(1):369.
[41] ZHU H, DING X, WANG C, et al. Preparation of rare earth-doped nano-fluorescent materials in the second near-infrared region and their application in biological imaging. J Mater Chem B. 2024;12(8):1947-1972.
[42] LIU Y, LI Y, KOO S, et al. Versatile Types of Inorganic/Organic NIR-IIa/IIb Fluorophores: From Strategic Design toward Molecular Imaging and Theranostics. Chem Rev. 2022;122(1):209-268.
[43] WANG Z, WANG X, WAN JB, et al. Optical Imaging in the Second Near Infrared Window for Vascular Bioimaging. Small. 2021;17(43): e2103780.
[44] WANG Q, TIAN L, XU J, et al. Multifunctional supramolecular vesicles for combined photothermal/photodynamic/hypoxia-activated chemotherapy. Chem Commun (Camb). 2018;54(73):10328-10331.