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An improved in vitro photochemical internalization protocol for 3D spheroid cultures

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Abstract

Photochemical internalization (PCI) is a modified form of photodynamic therapy (PDT) that enhances the efficacy of therapeutic agents in a site and temporal specific manner in both in vitro and in vivo publications. The purpose of the study reported here was to evaluate the benefits of a modified PCI protocol in a 3D rat glioma spheroid model. In the modified protocol, F98 glioma cells were incubated with photosensitizer (AlPcS2a) prior to spheroid generation, as opposed to post-spheroid formation photosensitizer exposure commonly used in conventional protocols. The efficacy of both bleomycin and doxorubicin PCI was evaluated using either the conventional or modified protocols. The formed spheroids were then exposed to light treatment from a diode laser,  λ= 670 nm. Spheroid growth was monitored for a period of 14 days. The results of spheroid growth assays showed that there was no statistically significant difference in PCI efficacy between the conventional and modified protocols for both of the drugs tested. The direct PDT effect was significantly reduced using the modified protocol. Therefore, due to its several advantages, the modified protocol is recommended for evaluating the efficacy of PCI in tumor spheroid models.

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References

  1. 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 

  2. 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 Med 9(2):528

    Article  CAS  Google Scholar 

  3. Nichols MG, Foster TH (1994) Oxygen diffusion and reaction kinetics in the photodynamic therapy of multicell tumour spheroids. Phys Med Biol 39:61–2181

    Article  Google Scholar 

  4. Bonsted A, Engesaeter BØ, Høgset A, Berg K (2006) Photochemically enhanced adenoviral transduction in a multicellular environment. Photochem Photobiol Sci 5:411–421

    Article  CAS  Google Scholar 

  5. Ivascu A, Kubbies M (2006) Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis. J Biomol Screen 11:922–932

    Article  CAS  Google Scholar 

  6. 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 

  7. Peng W, Samplonius DF, de Visscher S, Roodenburg JL, Helfrich W, Witjes MJ (2014) Photochemical internalization (PCI)-mediated enhancement of bleomycin cytotoxicity by liposomal mTHPC formulations in human head and neck cancer cells. Lasers Surg Med 46:650–658

    Article  Google Scholar 

  8. Lai PS, Lou PJ, Peng CL, Pai CL, Yen WN, Huang MY, Young TH, Shieh MJ (2007) Doxorubicin delivery by polyamidoamine dendrimer conjugation and photochemical internalization for cancer therapy. J Control Release 122:39–46

    Article  CAS  Google Scholar 

  9. Prasmickaite L, Høgset A, Selbo PK, Engesæter BØ, Hellum M, Berg K (2002) Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy. Br J Cancer 86:652–657

    Article  CAS  Google Scholar 

  10. De Bruin KG, Fella C, Ogris M, Wagner E, Ruthardt N, Bräuchle C (2008) Dynamics of photo-induced endosomal release of polyplexes. J Control Release 130:175–182

    Article  Google Scholar 

  11. Wang F, Zamora G, Sun CH, Trinidad A, Chun C, Kwon YJ, Berg K, Madsen SJ, Hirschberg H (2014) Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced nonviral transfection of the cytosine deaminase suicide gene. J Neurooncol 118(1):2937

    Article  Google Scholar 

  12. Soubéran A, Tchoghandjian A (2020) Practical review on preclinical human 3D glioblastoma models: advances and challenges for clinical translation. Cancers Basel 12:2347

    Article  Google Scholar 

  13. Zanoni M, Cortesi M, Zamagni A, Arienti C, Pignatta S, Tesei A (2020) Modeling neoplastic disease with spheroids and organoids. J Hematol Oncol 13:97

    Article  Google Scholar 

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Funding

The authors are grateful for support from the Norwegian Radium Hospital Research Foundation. Grant nr. SE.1305 and 1503. Steen Madsen was supported, in part, by the Tony and Renee Marlon Charitable Foundation.

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Authors and Affiliations

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

    Lina Nguyen & Henry Hirschberg

  2. Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, NV, USA

    Steen J. Madsen

  3. Department of Radiation Biology, Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway

    Kristian Berg

Authors
  1. Lina Nguyen
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  2. Steen J. Madsen
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  3. Kristian Berg
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  4. Henry Hirschberg
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Correspondence to Lina Nguyen.

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All of the authors declare no competing interests.

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Nguyen, L., Madsen, S.J., Berg, K. et al. An improved in vitro photochemical internalization protocol for 3D spheroid cultures . Lasers Med Sci 36, 1567–1571 (2021). https://doi.org/10.1007/s10103-021-03332-y

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  • DOI: https://doi.org/10.1007/s10103-021-03332-y

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