Cold to Hot: Rational Design of Minimalist Multifunctional Photo-Immunotherapy Nanoplatform toward Boosting Immunotherapy Capability

Di Zhang, Jing Zhang, Qian Li, Aixin Song, Zhonghao Li, Yuxia Luan
ACS Applied Materials & Interfaces 2019 August 20
The concept of integrating immunogenic cell death (ICD) with tailoring immunosuppressive tumor microenvironment (TME) is promising for immunotherapy. Photothermal therapy (PTT) could efficiently induce ICD while indoleamine 2,3-dioxygenase (IDO) inhibitor could convert "cold" TME. Therefore, combination of PTT and IDO inhibitor is an attractive approach for immunotherapy. Unfortunately, combination of PTT and IDO inhibitor for tumor therapy is rarely reported. Herein, organic photothermal agent IR820 and IDO inhibitor 1-methyl-tryptophan (1MT) were, for the first time, designed to be an all-role-in-one molecule nanoplatform via molecular engineering strategy. The designed IR820-1MT molecule could self-assemble into nanoparticles with remarkably high dual-therapeutic agent loading (88.8 wt%). Importantly, poor water solubility of 1MT as well as inadequate target and short lifetime of IR820 were all well solved within as-prepared IR820-1MT nanoparticles. The laser-triggered IR820-1MT nanoparticles remarkably enhanced accumulation of cytotoxic T cells (CTLs), helper T cells (Ths), memory T cells and simultaneously suppressed proportion of regulatory T cells (Tregs), resulting in excellent immunotherapy against tumor metastasis and recurrence. Our molecular engineering strategy provides a promising alternative option for design of robust immunotherapy weapon against tumor metastasis and recurrence.

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