Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers.
The combination of light and photosensitizers for phototherapeutic interventions, such as photodynamic therapy, has transformed medicine and biology. However, the shallow penetration of light into tissues and the reliance on tissue oxygenation to generate cytotoxic radicals have limited the method to superficial or endoscope-accessible lesions. Here we report a way to overcome these limitations by using Cerenkov radiation from radionuclides to activate an oxygen-independent nanophotosensitizer, titanium dioxide (TiO2). We show that the administration of transferrin-coated TiO2 nanoparticles and clinically used radionuclides in mice and colocalization in tumours results in either complete tumour remission or an increase in their median survival. Histological analysis of tumour sections showed the selective destruction of cancerous cells and high numbers of tumour-infiltrating lymphocytes, which suggests that both free radicals and the activation of the immune system mediated the destruction. Our results offer a way to harness low-radiance-sensitive nanophotosensitizers to achieve depth-independent Cerenkov-radiation-mediated therapy.
Department of Radiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Nalinikanth
0000000300664563
N
Kotagiri
Department of Radiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Gail P
GP
Sudlow
Department of Radiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Walter J
WJ
Akers
Department of Radiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Samuel
S
Achilefu
D065638:Absorption, Radiation; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004574:Electromagnetic Fields; D005260:Female; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*; D011829:Radiation Dosage; D012542:Scattering, Radiation; D014025:Titanium / Q000737:chemistry / Q000627:therapeutic use*
D017319:Photosensitizing Agents; C009495:titanium dioxide; D014025:Titanium