Bypassing the Immunosuppression of Myeloid‐Derived Suppressor Cells by Reversing Tumor Hypoxia Using a Platelet‐Inspired Platform

Abstract

Myeloid-derived suppressor cells (MDSCs) are garnering increasing attention given their role in tumor development. Herein, a nano-enabled strategy is demonstrated for the eradication of tumor-infiltrated MDSCs by reversing hypoxia. Oxygen-independent photodynamic bismuth tungstate nanoparticles (Bi 2 WO 6 NPs) are loaded into reactive oxygen species (ROS) responsive platelet membranes (PMs) to form a hybrid (PM-BiW NPs). P-Selectin on PMs endows PM-BiW NPs with selectivity toward cancer cells. Once in the tumor, laser illumination stimulates the Bi 2 WO 6 NPs photothermally and photodynamically, which produces enormous quantities of hydroxyl radicals. These hydroxyl radicals help rupture the PM and mitigate hypoxia with the assistance of ionizing radiation. This effectively remodels the tumor micro environment toward one disfavoring the recruitment of MDSCs and contributes to better prognosis. To better understand the mechanism, the expression levels of a set of markers are monitored. It is found that the downregulations of hypoxia-inducible factor-1α, ectonucleoside triphosphate diphosphohydrolase 2, and adenosine-5-phosphoricacid are behind the blocked infiltration of MDSCs. This platform strategy offers a promising approach to overcome the immunosuppression caused by MDSCs through a trimodal therapy integrating the power of photothermal and photodynamic therapy in addition to radiation therapy. Scheme 1. Working principle of PM-BiW NPs. In radical-free RT treatment, oxygen is essential for reaction with the broken end of DNA to augment the damage to an extent beyond the cells' repairing power. This leads to a deteriorated hypoxia condition that helps to recruit MDSCs and inhibits the function of CTLs. For PTT/PDT/RT treatment, in the presence of PM-BiW • OH radicals generated upon illumination can cause the destruction of ROS-responsive PM, followed by their release into cytosol where they behave as a sensitizer for irradiation. As the generation of • OH is fueled by H 2 O, there is no longer oxygen consumption. Thus, the tumor microenvironment is remodeled in such a way that the recruitment of MDSCs is disfavored. This also helps the CTLs respond to stress condition to act effectively against tumors.www.afm-journal.de www.advancedsciencenews.com (3 of 18)

γ-Glutamyl transpeptidase-activatable near-infrared nanoassembly for tumor fluorescence imaging-guided photothermal therapy

“…Then, NRh-G-NPs (5.8 μg/mL) were added, and the cells were incubated at 37 °C for another 20 min. After replacing the medium, the fluorescence images were captured on a confocal fluorescence microscope 37 , 38 .…”

Recent advances on Bi2WO6-based photocatalysts for environmental and energy applications

“…These results reveal the broad prospects of Bi2WO6 nanoparticles in the treatment of cancer through PTT and oxygen-free PDT. Furthermore, the complex of Bi2WO6 nanoparticles and platelet membranes were synthesized, which overcame the shortcomings of Bi2WO6 alone and realized long-term circulation in the blood and penetration into deep tumors [88]. The working principle of the hybrid for tumor treatment was shown in Fig.…”

“…Oil bath X-ray irradiation; /; / Tumor volume: ~30% of its original size [88] Similar to metal doping, nonmetal doping also shows a positive effect on improving the photocatalytic efficiency. Photocatalytic activity of N doped Bi2WO6 was explored by Hoang et al [119] via a two-step microwave-assisted and hydrothermal process.…”

Sono/Photodynamic Nanomedicine‐Elicited Cancer Immunotherapy

“…Hu et al. [ 141 ] employed a bismuth tungstate (Bi 2 WO 6 ) NP, which can induce both PTT and oxygen‐independent type‐I PDT, to fabricate a platelet membrane (PM)‐coated tumor‐homing nanoplatform. Unlike type‐II PDT that consumes O 2 , generation of •OH in type‐I PDT is fueled by H 2 O.…”