Nanoconjugates to enhance PDT-mediated cancerimmunotherapy by targeting the indoleamine-2,3-dioxygenase pathway

作者：Xueyuan Yang, Weizhong Zhang, Wen Jiang, Anil Kumar, Shiyi Zhou, Zhengwei Cao, Shuyue Zhan, Wei Yang, Rui Liu, Yong Teng, Jin Xie · 发表于：Journal of Nanobiotechnology · 年份：2021 · DOI：10.1186/s12951-021-00919-z · 被引用次数：43 · 研究领域：Tryptophan and brain disorders、Cancer, Stress, Anesthesia, and Immune Response、Nanoplatforms for cancer theranostics

Abstract Background Photodynamic therapy (PDT) may elicit antitumor immune response in addition to killing cancer cells. However, PDT as a monotherapy often fails to induce a strong immunity. Immune checkpoint inhibitors, which selectively block regulatory axes, may be used in combination with PDT to improve treatment outcomes. Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme and an important meditator of tumor immune escape. Combination therapy with PDT and IDO-targeted immune checkpoint blockage is promising but has been seldom been explored. Methods Herein we report a composite nanoparticle that allows for simultaneous delivery of photosensitizer and IDO inhibitor. Briefly, we separately load ZnF 16 Pc, a photosensitizer, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, into ferritin and poly(lactide- co -glycolic)- block -poly(ethylene glycol) (PEG-PLGA) nanoparticles; we then conjugate these two compartments to form a composite nanoparticle referred to as PPF NPs. We tested combination treatment with PPF NPs first in vitro and then in vivo in B16F10-tumor bearing C57/BL6 mice. Results Our results showed that PPF NPs can efficiently encapsulate both ZnF 16 Pc and NLG919. In vivo studies found that the combination treatment led to significantly improved tumor suppression and animal survival. Moreover, the treatment increased tumor infiltration of CD8 + T cells, while reducing frequencies of MDSCs and Tregs. 30% of the animals showed complete tumor...