Journal
SMALL
Volume 14, Issue 20, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201800678
Keywords
immunogenic cell death; neuroblastoma; photothermal therapy; Prussian blue nanoparticles; thermal dose
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Funding
- Alex's Lemonade Stand Foundation for Childhood Cancer
- George Washington University Cancer Center
- Sheikh Zayed Institute for Pediatric Surgical Innovation at Children's National Health System
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A thermal window of immunogenic cell death (ICD) elicited by nanoparticle-based photothermal therapy (PTT) in an animal model of neuroblastoma is described. In studies using Prussian blue nanoparticles to administer photothermal therapy (PBNP-PTT) to established localized tumors in the neuroblastoma model, it is observed that PBNP-PTT conforms to the more is better paradigm, wherein higher doses of PBNP-PTT generates higher cell/local heating and thereby more cell death, and consequently improved animal survival. However, in vitro analysis of the biochemical correlates of ICD (ATP, high-motility group box 1, and calreticulin) elicited by PBNP-PTT demonstrates that PBNP-PTT triggers a thermal window of ICD. ICD markers are highly expressed within an optimal temperature (thermal dose) window of PBNP-PTT (63.3-66.4 degrees C) as compared with higher (83.0-83.5 degrees C) and lower PBNP-PTT (50.7-52.7 degrees C) temperatures, which both yield lower expression. Subsequent vaccination studies in the neuroblastoma model confirm the in vitro findings, wherein PBNP-PTT administered within the optimal temperature window results in long-term survival (33.3% at 100 d) compared with PBNP-PTT administered within the higher (0%) and lower (20%) temperature ranges, and controls (0%). The findings demonstrate a tunable immune response to heat generated by PBNP-PTT, which should be critically engaged in the administration of PTT for maximizing its therapeutic benefits.
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