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2016 ; 138
(51
): 16686-16695
Nephropedia Template TP
gab.com Text
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English Wikipedia
Photodynamic Therapy Mediated by Nontoxic Core-Shell Nanoparticles Synergizes
with Immune Checkpoint Blockade To Elicit Antitumor Immunity and Antimetastatic
Effect on Breast Cancer
#MMPMID27976881
Duan X
; Chan C
; Guo N
; Han W
; Weichselbaum RR
; Lin W
J Am Chem Soc
2016[Dec]; 138
(51
): 16686-16695
PMID27976881
show ga
An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the
battle against cancer, especially the metastatic disease. Checkpoint
blockade-based immunotherapies have been shown to be extraordinarily effective
but benefit only the minority of patients whose tumors have been pre-infiltrated
by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with
the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation
with light directly by inducing apoptosis and/or necrosis and indirectly by
disrupting tumor vasculature and increasing tumor immunogenicity. Furthermore,
immunogenic ZnP@pyro photodynamic therapy (PDT) treatment sensitizes tumors to
checkpoint inhibition mediated by a PD-L1 antibody, not only eradicating the
primary 4T1 breast tumor but also significantly preventing metastasis to the
lung. The abscopal effects on both 4T1 and TUBO bilateral syngeneic mouse models
further demonstrate that ZnP@pyro PDT treatment combined with anti-PD-L1 results
in the eradication of light-irradiated primary tumors and the complete inhibition
of untreated distant tumors by generating a systemic tumor-specific cytotoxic T
cell response. These findings indicate that nanoparticle-mediated PDT can
potentiate the systemic efficacy of checkpoint blockade immunotherapies by
activating the innate and adaptive immune systems in tumor microenvironment.