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Indocyanine green-loaded microspheres as a near-infrared fluorescence marker for long-term localization of tumor sites

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Abstract

Purpose

Noninvasive and real-time detection of tumor sites is highly important for precision cancer surgery. In this study, we developed indocyanine green (ICG)-loaded microspheres as near-infrared (NIR) fluorescence markers for the noninvasive and long-term localization of tumor sites.

Methods

Microspheres were prepared using a water-in-oil-in-water method to encapsulate ICGs into small and multiple separated pores inside the microspheres. Microspheres containing different amounts of Poloxamer 188 were evaluated both in vitro and in vivo.

Results

Encapsulation of ICG and the human serum albumin (HSA) complex in the microspheres showed 25-fold higher fluorescence signals than ICG alone. The addition of 1% poloxamer 188 (P-188) to the oil phase resulted in the highest fluorescence signal from the microspheres. When ICG-HSA-loaded microspheres with 1% P-188 were subcutaneously injected into SKH-1 hairless mice, strong fluorescence signals from the injection sites were detected for up to 30 d without a significant reduction in the NIR fluorescence intensity.

Conclusion

Biocompatible ICG dye-loaded microspheres have great potential as long-term fluorescent markers for imaging-guided precision surgery.

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Data availability

All data generated or analysed during this study are included in this published article and its supplementary information file.

References

  • An F, Yang Z, Zheng M, Mei T, Deng G et al (2020) Rationally assembled albumin/indocyanine green nanocomplex for enhanced tumor imaging to guide photothermal therapy. J Nanobiotechnology 18:49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassinotti E, Al-Taher M, Antoniou SA, Arezzo A, Baldari L et al (2023) European Association for Endoscopic Surgery (EAES) consensus on indocyanine green (ICG) fluorescence-guided surgery. Surg Endosc 37:1629–1648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng X, Henick BS, Cheng K (2024) Anticancer therapy targeting cancer-derived extracellular vesicles. ACS Nano 18:6748–6765

    Article  CAS  PubMed  Google Scholar 

  • Choi Y, Kim SY, Kim SH, Park TG, Moon HT et al (2002) In vivo biocompatibility studies of poly(D, L-lactide)/poly(ethylene glycol)-poly(L-lactide) microspheres containing all-trans-retinoic acid. J Biomater Sci Polym Ed 13:301–322

    Article  CAS  PubMed  Google Scholar 

  • Cui W, Bei J, Wang S, Zhi G, Zhao Y et al (2005) Preparation and evaluation of poly(L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography. J Biomed Mater Res B Appl Biomater 73:171–178

    Article  PubMed  Google Scholar 

  • Garbarino GM, Laracca GG, Lucarini A, Piccolino G, Mercantini P et al (2022) Laparoscopic versus open surgery for gastric cancer in western countries: a systematic review and meta-analysis of short- and long-term outcomes. J Clin Med 11:3590

    Article  PubMed  PubMed Central  Google Scholar 

  • Gnant M (2022) Breast surgery after neoadjuvant therapy. Curr Opin Oncol 34:643–646

    Article  PubMed  Google Scholar 

  • Hartmann S, Reimer T, Gerber B, Stubert J, Stengel B et al (2018) Wire localization of clip-marked axillary lymph nodes in breast cancer patients treated with primary systemic therapy. Eur J Surg Oncol 44:1307–1311

    Article  PubMed  Google Scholar 

  • Jang HJ, Song MG, Park CR, Youn HW, Lee YS et al (2023) Imaging of indocyanine green-human serum albumin (ICG-HSA) complex in secreted protein acidic and rich in cysteine (SPARC)-expressing glioblastoma. Int J Mol Sci 24:850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim HJ, Kim HY, Lee EY, Choi BK, Jang HC et al (2020) A quenched annexin V-fluorophore for the real-time fluorescence imaging of apoptotic processes in vitro and in vivo. Adv Sci 7:2002988

    Article  CAS  Google Scholar 

  • Kosaka N, Ogawa M, Choyke PL, Kobayashi H (2009) Clinical implications of near-infrared fluorescence imaging in cancer. Future Oncol 5(9):1501–1511

    Article  PubMed  Google Scholar 

  • Lee SS, Kim HJ, Sohn DK, Eom JB, Seo YS et al (2020) Indocyanine green-loaded injectable alginate hydrogel as a marker for precision cancer surgery. Quant Imaging Med Surg 10:779–788

    Article  PubMed  PubMed Central  Google Scholar 

  • Madhi H, Lee JS, Choi YE, Li Y, Kim MH et al (2022) FOXM1 inhibition enhances the therapeutic outcome of lung cancer immunotherapy by modulating PD-L1 expression and cell proliferation. Adv Sci 9:e2202702

    Article  Google Scholar 

  • Miliotou AN, Papadopoulou LC (2018) CAR T-cell therapy: a new era in cancer immunotherapy. Curr Pharm Biotechnol 19:5–18

    Article  PubMed  Google Scholar 

  • Mylonaki I, Allémann E, Delie F, Jordan O (2018) Imaging the porous structure in the core of degrading PLGA microparticles: the effect of molecular weight. J Control Release 286:231–239

    Article  CAS  PubMed  Google Scholar 

  • NtziachristosV BC, Weissleder R (2003) Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol 13:195–208

    Article  Google Scholar 

  • Pang Q, Duan L, Jiang Y, Liu H (2021) Oncologic and long-term outcomes of enhanced recovery after surgery in cancer surgeries—a systematic review. World J Surg Oncol 19:191

    Article  PubMed  PubMed Central  Google Scholar 

  • Philip R, Penzkofer A, Bäumler W, Szeimies RM, Abels C (1996) Absorption and fluorescence spectroscopic investigation of indocyanine green. J Photochem Photobio A 96:137–148

    Article  CAS  Google Scholar 

  • Philpotts LE, Lee CH (2002) Clip migration after 11-gauge vacuum-assisted stereotactic biopsy: case report. Radiology 222:794–796

    Article  PubMed  Google Scholar 

  • Raj A, Babu A, Kothandan VK, Park IK, Hwang SR (2023) Development of nano-immunotherapy for cancer treatment: achievements and scopes. J Pharm Investig 53:827–844

    Article  CAS  Google Scholar 

  • Reinhart MB, Huntington CR, Blair LJ, Heniford BT, Augenstein VA (2016) Indocyanine green: historical context, current applications, and future considerations. Surg Innov 23:166–175

    Article  PubMed  Google Scholar 

  • Rhew K, Chae YJ, Chang JE (2022) Progress and recent trends in photodynamic therapy with nanoparticles. J Pharm Investig 52:587–599

    Article  Google Scholar 

  • Saxena V, Sadoqi M, Shao J (2003) Degradation kinetics of indocyanine green in aqueous solution. J Pharm Sci 92:2090–2097

    Article  CAS  PubMed  Google Scholar 

  • Song G, Petschauer JS, Madden AJ, Zamboni WC (2014) Nanoparticles and the mononuclear phagocyte system: pharmacokinetics and applications for inflammatory diseases. Curr Rheumatol Rev 10:22–34

    Article  CAS  PubMed  Google Scholar 

  • Zandstra J, Hiemstra C, Petersen AH, Zuidema J, Beuge MM et al (2014) Microsphere size influences the foreign body reaction. Eur Cell Mater 28:335–347

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: RS-2020-KD000107) and a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C3011436).

Funding

Funding was provided by Korea Medical Device Development Fund (Grant No. RS-2020-KD000107), National Research Foundation of Korea (Grant No. 2022R1A2C3011436).

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Correspondence to Yongdoo Choi.

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All authors (HJ Kim and Y Choi) declare that they have no conflict of interest.

Research involving in human and animal rights

All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of the National Cancer Center Research Institute (IACUC approval no. NCC-21-638).

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Kim, HJ., Choi, Y. Indocyanine green-loaded microspheres as a near-infrared fluorescence marker for long-term localization of tumor sites. J. Pharm. Investig. (2024). https://doi.org/10.1007/s40005-024-00685-8

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