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Photosensitizer delivery by fibrin glue: potential for bypassing the blood-brain barrier

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Abstract

Fibrin glue (FG) has potential as a delivery vehicle for photosensitizer directly to the resection cavity, so it may bypass the blood-brain barrier (BBB) and increase the concentration of successfully delivered photosensitizer. A specialized form of photodynamic therapy (PDT), photochemical internalization (PCI), which involves both photosensitizer and chemotherapeutic agent internalization, can locally inhibit the growth of cells. This will allow the reduction of recurrence of malignant gliomas around surgical resection. This study will look at the efficacy of FG loaded with drugs in mediating both PDT and PCI in inhibiting 3-dimensional tumor spheroid growth in vitro. Experiments were conducted on spheroids comprised of F98 glioma cells using photosensitizer AlPcS2a and chemotherapeutic drug bleomycin (BLM). At 2-, 24-, 48-, and 72-h increments, supernatant covering an FG layer within a well was collected and replaced by fresh medium, then added to spheroid-containing wells, which contained the respective chemicals for PDT and PCI. The wells were then exposed to light treatment from a diode laser, and after, spheroid growth was monitored for a period of 14 days. Significant spheroid growth inhibition was observed in both PDT and PCI modalities, but was far greater in PCI. Additionally, complete growth suppression was achieved via PCI at the highest radiant exposure. Achieving a slow photosensitizer release, significant F98 spheroid inhibition was observed in FG-mediated PDT and PCI. The present study showed BLM-PCI was the most efficacious of the two modalities.

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References

  1. Chamberlain MC (2011) Radiographic patterns of relapse in glioblastoma. J Neuro-Oncol 101:319–323

    Article  Google Scholar 

  2. Dobelbower MC, Burnett OL III, Nordal RA, Nabors LB, Markert JM, Hyatt MD, Fiveash JB (2011) Patterns of failure for glioblastoma multiforme following concurrent radiation and temozolomide. J Med Imaging Radiat Oncol 55:77–81

    Article  Google Scholar 

  3. Robertson CA, Hawkins Evans D, Abrahamse H (2009) Photodynamic therapy (PDT): a short review on cellular mechanisms and cancer research applications for PDT. J Photochem Photobiol B Biol 96:1–8

    Article  CAS  Google Scholar 

  4. Abrahamse H, Hamblin MR (2016) New photosensitizers for photodynamic therapy. Biochem J 473:347–364

    Article  CAS  Google Scholar 

  5. Berg K, Selbo PK, Prasmickaite L, Tjelle TE, Sandvig K, Moan J, Gaudernack G, Fodstad O, Kjølsrud S, Anholt H, Rodal GH, Rodal SK, Høgset A (1999) Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Res 59:1180–1183

    CAS  PubMed  Google Scholar 

  6. Selbo PK, Weyergang A, Høgset A, Norum OJ, Berstad MB, Vikdal M, Berg K (2010) Photochemical internalization provides time-and space-controlled endolysosomal escape of therapeutic molecules. J Control Release 148:2–12

    Article  CAS  Google Scholar 

  7. Mathews MS, Blickenstaff JW, Shih EC, Zamora G, Vo V, Sun CH, Hirschberg H, Madsen SJ (2012) Photochemical internalization of bleomycin for glioma treatment. J Biomed Opt 17:058001

    Article  Google Scholar 

  8. Sultan AA, Jerjes W, Berg K, Høgset A, Mosse CA, Hamoudi R, Hamdoon Z, Simeon C, Carnell D, Forster M, Hopper C (2016) Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial. Lancet Oncol 17:1217–1229

    Article  CAS  Google Scholar 

  9. Jerjes W, Theodossiou TA, Hirschberg H, Høgset A, Weyergang A, Selbo PK, Hamdoon Z, Hopper C, Berg K (2020) Photochemical internalization for intracellular drug delivery. From basic mechanisms to clinical research. J Clin 9:528

    CAS  Google Scholar 

  10. Vasilev A, Sofi R, Rahman R, Smith SJ, Teschemacher AJ, Kasparov S (2020) Using light for therapy of glioblastoma multiforme (GBM). Brain Sci 10:75

    Article  CAS  Google Scholar 

  11. Cramer SW, Chen CC (2020) Photodynamic therapy for the treatment of glioblastoma. Front Surg 6:81

    Article  Google Scholar 

  12. Madsen SJ, Angell-Petersen E, Spetalen S, Carper SW, Ziegler SA, Hirschberg H (2006) Photodynamic therapy of newly implanted glioma cells in the rat brain. Lasers Surg Med 38:540–548

    Article  Google Scholar 

  13. Yoshida H, Yamaoka Y, Shinoyama M, Kamiya A (2000) Novel drug delivery system using autologous fibrin glue--release properties of anti-cancer drugs. Biol Pharm Bull 23:371–374

    Article  CAS  Google Scholar 

  14. Spicer PP, Mikos AG (2010) Fibrin glue as a drug delivery system. J Control Release 148:49–55

    Article  CAS  Google Scholar 

  15. Anai S, Hide T, Takezaki T, Kuroda J, Sinojima N, Makino K, Nakamura H, Yano S, Kuratsu J (2014) Antitumor effect of fibrin glue containing temozolomide against malignant glioma. Cancer Sci 105:583–591

    Article  CAS  Google Scholar 

  16. Bastiancich C, Danhier P, Préat V, Danhier F (2016) Anticancer drug-loaded hydrogels as drug delivery systems for the local treatment of glioblastoma. J Control Release 243:29–42

    Article  CAS  Google Scholar 

  17. Bastiancich C, Lemaire L, Bianco J, Franconi F, Danhier F, Preat V, Bastiat G, Lagarce F (2018) Evaluation of lauroyl-gemcitabine-loaded hydrogel efficacy in glioblastoma rat models. Nanomedicine 13:1999–2013

    Article  CAS  Google Scholar 

  18. Bastiancich C, Bozzato E, Luyten U, Danhier F, Bastiat G, Préat V (2019) Drug combination using an injectable nanomedicine hydrogel for glioblastoma treatment. Int J Pharm 559:220–227

    Article  CAS  Google Scholar 

  19. Sierra DH (1993) Fibrin sealant adhesive systems: a review of their chemistry, material properties and clinical applications. J Biomater Appl 7:309–352

    Article  CAS  Google Scholar 

  20. Johannesen TB, Watne K, Lote K, Norum J, Henning JR, Tvera K, Hirschberg H (1999) Intracavity fractionated balloon brachytherapy in glioblastoma. Acta Neurchiurica 141:127–133

    Article  CAS  Google Scholar 

  21. Madsen SJ, Sun CH, Tromberg B, Hirschberg H (2001) Development of a novel balloon applicator for optimizing light delivery in photodynamic therapy. Lasers Surg Med 29:406–412

    Article  CAS  Google Scholar 

  22. Eljamel MS, Goodman C, Moseley H (2008) ALA and Photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre phase III randomized controlled trial. Lasers Med Sci 23:361–367

    Article  Google Scholar 

  23. Bisland SK, Lilge L, Lin A, Rusnov R, Wilson BC (2004) Metronomic photodynamic therapy as a new paradigm for photodynamic therapy: rationale and preclinical evaluation of technical feasibility for treating malignant brain tumors. Photochem Photobiol 80:22–30

    Article  CAS  Google Scholar 

  24. Hirschberg H, Sorensen DR, Angell-Petersen E, Peng Q, Tromberg B, Sun CH, Spetalen S, Madsen S (2006) Repetitive photodynamic therapy of malignant brain tumors. J Environ Pathol Toxicol Oncol 25:261–279

    Article  CAS  Google Scholar 

  25. Guo HW, Lin LT, Chen PH, Ho MH, Huang WT, Lee YJ, Chiou SH, Hsieh YS, Dong CY, Wang HW (2015) Low-fluence rate, long duration photodynamic therapy in glioma mouse model using organic light emitting diode (OLED). Photodiagn Photodyn Ther 12:504–510

    Article  CAS  Google Scholar 

  26. Shin D, Nguyen L, Le MT, Ju D, Le JN, Berg K, Hirschberg H (2019) The effects of low irradiance long duration photochemical internalization on glioma spheroids. Photodiagn Photodyn Ther 26:442–447

    Article  CAS  Google Scholar 

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Funding

This work received support from the Norwegian Radium Hospital Research Foundation (Grant nr. SE.1305 and 1503).

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Authors and Affiliations

  1. Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd, Irvine, CA, 92617, USA

    Lina Nguyen, Eric O. Potma, Jimmy N. Le, Julie Johnson, Gabrielle Romena & Henry Hirschberg

  2. Pathology Clinic, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway

    Qian Peng

  3. Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway

    Kristian Berg

Authors
  1. Lina Nguyen
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  2. Eric O. Potma
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  3. Jimmy N. Le
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Correspondence to Lina Nguyen.

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Nguyen, L., Potma, E.O., Le, J.N. et al. Photosensitizer delivery by fibrin glue: potential for bypassing the blood-brain barrier. Lasers Med Sci 36, 1031–1038 (2021). https://doi.org/10.1007/s10103-020-03140-w

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  • DOI: https://doi.org/10.1007/s10103-020-03140-w

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