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Combinational phototherapy and hypoxia-activated chemotherapy favoring antitumor immune responses

Authors Ma B, Sheng J, Wang P, Jiang Z, Borrathybay E

Received 29 January 2019

Accepted for publication 14 April 2019

Published 20 June 2019 Volume 2019:14 Pages 4541—4558

DOI https://doi.org/10.2147/IJN.S203383

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Editor who approved publication: Dr Mian Wang


Beibei Ma,1,* Jie Sheng,1,2,* Ping Wang,1 Zhongying Jiang,1,2 Entomack Borrathybay3

1College of Electronic and Information Engineering, Yili Normal University, Micro-nano Electric Sensing Technology and Bionic Devices Key Laboratory, Yining 835000, People’s Republic of China; 2Physics School of Nanjing University, Laboratory of Solid State Microstructures, Nanjing 210093, People’s Republic of China; 3College of Biology and Geography Sciences, Yili Normal University, Yining, Xinjiang, 835000, People’s Republic of China

*These authors contributed equally to this work

Background: Tumor metastasis is responsible for most cancer death worldwide, which lacks curative treatment.
Purpose: The objective of this study was to eliminate tumor and control the development of tumor metastasis.
Methods: Herein, we demonstrated a smart nano-enabled platform, in which 2-[2-[2-chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2h-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) and tirapazamine (TPZ) were co-loaded in poly(ϵ-caprolactone)-poly(ethylene glycol) (PEG-PCL) to form versatile nanoparticles (PEG-PCL-IR780-TPZ NPs).
Results: The intelligence of the system was reflected in the triggered and controlled engineering. Specially, PEG-PCL not only prolonged the circulation time of IR780 and TPZ but also promoted tumor accumulation of nanodrugs through enhanced permeability and retention (EPR) effect. Moreover, reactive oxygen species (ROS) generated by IR780 armed by an 808 nm laser irradiation evoked a cargo release. Meanwhile, IR780, as a mitochondria-targeting phototherapy agent exacerbated tumor hypoxic microenvironment and activated TPZ for accomplishing hypoxia-activated chemotherapy. Most significantly, IR780 was capable of triggering immunogenic cell death (ICD) during the synergic treatment. ICD biomarkers as a “danger signal” accelerated dendritic cells (DCs) maturation, and subsequently activated toxic T lymphocytes.
Conclusion: Eventually, antitumor immune responses stimulated by combinational phototherapy and hypoxia-activated chemotherapy revolutionized the current landscape of cancer treatment, strikingly inhibiting tumor metastasis and providing a promising prospect in the clinical application.

Keywords: phototherapy, hypoxia-activated chemotherapy, IR780, tirapazamine, antitumor immune responsive, metastasis

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