posted on 2020-11-25, 10:13authored byLin-Ping Zhao, Rong-Rong Zheng, Jia-Qi Huang, Xia-Yun Chen, Fu-An Deng, Yi-Bin Liu, Chu-Yu Huang, Xi-Yong Yu, Hong Cheng, Shi-Ying Li
Self-delivery of photosensitizer
and immune modulator to tumor
site is highly recommendable to improve the photodynamic immunotherapy
yet remains challenging. Herein, self-delivery photoimmune stimulators
(designated as iPSs) are developed for photodynamic sensitized tumor
immunotherapy. Carrier-free iPSs are constructed by optimizing the
noncovalent interactions between the pure drugs of chlorine e6 (Ce6)
and NLG919, which avoid the excipients-raised toxicity and immunogenicity.
Intravenously administrated iPSs prefer to passively accumulate on
tumor tissues for a robust photodynamic therapy (PDT) with the induction
of immunogenetic cell death (ICD) cascade to activate cytotoxic T
lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile,
the concomitant delivery of NLG919 inhibits the activation of indoleamine
2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment.
Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently
inhibit the primary and distant tumor growth with a low system toxicity,
which would shed light on the development of self-delivery nanomedicine
for clinical transformation in tumor precision therapy.