Single low-dose
irradiation enhances delivery and efficacy of dual
Pd-NP and C16proMMAE treatment. (a) Based on published
experimental data (see Table S3), computational
modeling predicts how local 5 Gy irradiation, performed 72 h prior
to NP injection, impacts tumoral NP accumulation and prodrug activation
(n = 24 optimizations; means ± s.e.m.). (b–c)
HT1080 tumor cells and the accumulation of PLGA-PEG NP were compared
with or without irradiation as modeled in (a), shown by confocal fluorescence
microscopy in live tumors (b; n ≥ 3, scale
bar 100 μm), and flow cytometry of excised and digested tumors
(c; n ≥ 4), 24 h post-treatment with NP. (d–e)
HT1080 tumor xenografts were treated as in Figure 6a, but with addition of a single-dose of
5 Gy irradiation locally to the tumor site (un-irradiated groups are
re-shown for reference; n ≥ 5, means ±
s.e.m). Corresponding changes in the volumes of individual tumors
were quantified at day 7 (n ≥ 5, means ±
s.e.m; two-tailed t tests).