Breaking the depth dependency of phototherapy with Cerenkov radiation and
low-radiance-responsive nanophotosensitizers
#MMPMID25751304
Kotagiri N
; Sudlow GP
; Akers WJ
; Achilefu S
Nat Nanotechnol
2015[Apr]; 10
(4
): 370-9
PMID25751304
show ga
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.
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