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

Lasers Med Sci. 2021 Jul;36(5):1031-1038. doi: 10.1007/s10103-020-03140-w. Epub 2020 Oct 30.


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.

Keywords: Bleomycin; Fibrin glue; PCI; Photochemical internalization.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Biological Transport
  • Bleomycin / chemistry
  • Bleomycin / metabolism
  • Bleomycin / pharmacology
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Cell Line, Tumor
  • Drug Carriers / chemistry*
  • Fibrin Tissue Adhesive / chemistry*
  • Humans
  • Indoles / chemistry
  • Indoles / metabolism
  • Indoles / pharmacology
  • Lasers, Semiconductor
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / metabolism*
  • Photosensitizing Agents / pharmacology


  • Antineoplastic Agents
  • Drug Carriers
  • Fibrin Tissue Adhesive
  • Indoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • Bleomycin
  • aluminum phthalocyanine disulfonate