Oxygen-Based Nanocarriers to Modulate Tumor Hypoxia for Ameliorated Anti-Tumor Therapy: Fabrications, Properties, and Future Directions.

Xianqiang Li,Yue Wu,Tiantian Ye,Rui Zhang,Shujun Wang,Wei Bai

doi:10.3389/fmolb.2021.683519

Xianqiang Li, Yue Wu + Show 4 more

Open Access

https://doi.org/10.3389/fmolb.2021.683519

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Abstract

Over the past five years, oxygen-based nanocarriers (NCs) to boost anti-tumor therapy attracted tremendous attention from basic research and clinical practice. Indeed, tumor hypoxia, caused by elevated proliferative activity and dysfunctional vasculature, is directly responsible for the less effectiveness or ineffective of many conventional therapeutic modalities. Undeniably, oxygen-generating NCs and oxygen-carrying NCs can increase oxygen concentration in the hypoxic area of tumors and have also been shown to have the ability to decrease the expression of drug efflux pumps (e.g., P-gp); to increase uptake by tumor cells; to facilitate the generation of cytotoxic reactive oxide species (ROS); and to evoke systematic anti-tumor immune responses. However, there are still many challenges and limitations that need to be further improved. In this review, we first discussed the mechanisms of tumor hypoxia and how it severely restricts the therapeutic efficacy of clinical treatments. Then an up-to-date account of recent progress in the fabrications of oxygen-generating NCs and oxygen-carrying NCs are systematically introduced. The improved physicochemical and surface properties of hypoxia alleviating NCs for increasing the targeting ability to hypoxic cells are also elaborated with special attention to the latest nano-technologies. Finally, the future directions of these NCs, especially towards clinical translation, are proposed. Therefore, we expect to provide some valued enlightenments and proposals in engineering more effective oxygen-based NCs in this promising field in this comprehensive overview.

Highlights

The oxygen level of the human solid tumors is consistently less than the normal tissue that is socalled tumor hypoxia, which can be classified into two main categories
Results from their study suggested that tetra (p-benzoato) porphyrin (TBP) mediated photodynamic therapy (PDT) greatly boosted the a-PD-L1 therapy efficacy and elicited an abscopal effect in the treatment of colorectal cancer, which leads to more than 90% regression of tumors
We propose some of the research directions that should be given more attention in the future, which are based on the challenges and limitations as discussed in the previous section

Summary

INTRODUCTION

The oxygen level of the human solid tumors is consistently less than the normal tissue that is socalled tumor hypoxia, which can be classified into two main categories. Due to the presence of acute hypoxia (Figure 1B), HBO therapy was not successful (Brown and Wilson, 2004) To this end, many nanocarriers (NCs) are fabricated to overcome the inherent drawbacks of oxygen-based therapy via a high tumor-targeting property and thereby to provide an efficient, improved, and safer tumor treatment (Sahu et al, 2020). IMT utilizes neoantigens, expressed by tumor cells, recognized by innate and adaptive immune cells such as T lymphocytes to induce anti-tumor immune responses, thereby eliminating tumors, which includes non-specific immune stimulation, adoptive T-cell transfer, immune-checkpoint blockade, and vaccination strategies (e.g., sipuleucel-T for prostate cancer) This type of therapy does not involve the use of molecular oxygen, its clinical efficacy can be frustrated by a hypoxic TME through changing the function of host immune cells, as often suggested in the literature (Noman et al, 2015).

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