Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy.

Jinrong Peng,Wenting Li,Yanpeng Jia,Zhiyong Qian,Qian Yang,Ying Qu,Yao Xiao,Liwei Tan

doi:10.1002/advs.201700891

Abstract

The therapeutic outcome of photothermal therapy (PTT) remains impeded by the transparent depth of light. Combining PTT with immunotherapy provides strategies to solve this problem. Regulating metabolism‐related enzymes is a promising strategy to stimulate immune response. Here, a nanosystem (NLG919/IR780 micelles) with the properties of photothermal conversion and regulation of the tryptophan metabolic pathway is used to suppress the growth of the tumor margin beyond effective PTT and promote tumor PTT and immunotherapy. It is revealed that mild heat treatment promotes the growth of the tumor margin beyond effective PTT for the upregulation of heat shock protein (HSP), indoleamine 2,3‐dioxygenase (IDO), and programmed death‐ligand 1 (PD‐L1). The NLG919/IR780 micelles can effectively inhibit the activity of IDO but do not affect the level of IDO expression. NLG919/IR780 micelles can effectively accumulate in the tumor and can migrate to lymph nodes and the lymphatic system. In vivo antitumor studies reveal that NLG919/IR780 micelles effectively suppress the growth of tumor margin following PTT in primary tumors. NLG919/IR780 micelle‐mediated PTT and IDO inhibition further stimulate the activation of T lymphocytes, inhibiting the growth of distal tumors (abscopal effect). The results demonstrate that the NLG919/IR780 micelles combine PTT and immunotherapy and suppress the tumor margin as well as distal tumor growth post photothermal therapy.

Highlights

Introduction the transparent depth of lightCombining PTT with immunotherapy provides strategies to solve this problem
The results show that the tumor margin beyond effective PTT was proliferating faster than tumors not subjected to PTT (Figure 1B)
To efficiently inhibit the growth of the localized tumor and stimulate the host to generate an immune response to suppress the growth of the tumor margin beyond effective PTT and the distal tumor, we have developed a nanomedicine containing NIR photosensitizer (IR780)

Summary

Introduction

Introduction the transparent depth of lightCombining PTT with immunotherapy provides strategies to solve this problem. The emergence of nanomedicines provides an alternative strategy for the delivery of therapeutic agents.[1] The (NLG919/IR780 micelles) with the properties of photothermal conversion and regulation of the tryptophan metabolic pathway is used to suppress the growth of the tumor margin beyond effective PTT and promote tumor PTT and immunotherapy. In vivo antitumor studies reveal that NLG919/IR780 micelles effectively suppress the growth of tumor margin some nanoparticle-based systems can strengthen the immune response in tumor immunotherapy, which has attracted much attention.[8,9,10,11]

Objectives

Results

Conclusion