Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy.

Published on Jul 13, 2020in Theranostics11.556
路 DOI :10.7150/THNO.46076
Zijun Shen3
Estimated H-index: 3
(Qingdao University),
Junfei Xia13
Estimated H-index: 13
(Tufts University)
+ 6 AuthorsYong Sun14
Estimated H-index: 14
(Qingdao University)
Sources
Abstract
Photodynamic therapy (PDT) is a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species (ROS) and eliminate cancer cells under specific wavelength light irradiation. However, special tumor environments, such as those with overexpression of glutathione (GSH), which will consume PDT-mediated ROS, as well as hypoxia in the tumor microenvironment (TME) could lead to ineffective treatment. Moreover, PDT is highly light-dependent and therefore can be hindered in deep tumor cells where light cannot easily penetrate. To solve these problems, we designed oxygen-dual-generating nanosystems MnO2@Chitosan-CyI (MCC) for enhanced phototherapy. Methods: The TME-sensitive nanosystems MCC were easily prepared through the self-assembly of iodinated indocyanine green (ICG) derivative CyI and chitosan, after which the MnO2 nanoparticles were formed as a shell by electrostatic interaction and Mn-N coordinate bonding. Results: When subjected to NIR irradiation, MCC offered enhanced ROS production and heat generation. Furthermore, once endocytosed, MnO2 could not only decrease the level of GSH but also serve as a highly efficient in situ oxygen generator. Meanwhile, heat generation-induced temperature increase accelerated in vivo blood flow, which effectively relieved the environmental tumor hypoxia. Furthermore, enhanced PDT triggered an acute immune response, leading to NIR-guided, synergistic PDT/photothermal/immunotherapy capable of eliminating tumors and reducing tumor metastasis. Conclusion: The proposed novel nanosystems represent an important advance in altering TME for improved clinical PDT efficacy, as well as their potential as effective theranostic agents in cancer treatment.
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References43
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Photodynamic therapy (PDT), as one of the most powerful photo-therapeutic strategies for cancer treatment with minimum invasiveness, can effectively damage local tumor cells and significantly induce systemic antitumor immunity. However, current nanotechnology-assisted PDT-immunomodulators has either poor penetration for deep tumors or low singlet oxygen generation. Herein, we construct a novel theranostic nanocarrier (HA-PEG-CyI, HPC) by inducing the self-assembly of PEGylated CyI and attaching ...
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#9Yu Chen (UMB: University of Maryland, Baltimore)H-Index: 33
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Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory resul...
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#7Jian Chen (SEU: Southeast University)H-Index: 22
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