Enzyme-Loaded pH-Sensitive Photothermal Hydrogels for Mild-temperature-mediated Combinational Cancer Therapy.

Jindong Xia,Junjian Shen,Xiuhui Wang,Yue Wang,Xueqin Qing,Mengbin Ding,Ningyue Yu,Jingchao Li

doi:10.3389/fchem.2021.736468

Abstract

Photothermal therapy (PTT) that utilizes hyperthermia to ablate cancer cells is a promising approach for cancer therapy, while the generated high temperature may lead to damage of surrounding normal tissues and inflammation. We herein report the construction of glucose oxidase (GOx)-loaded hydrogels with a pH-sensitive photothermal conversion property for combinational cancer therapy at mild-temperature. The hydrogels (defined as CAG) were formed via coordination of alginate solution containing pH-sensitive charge-transfer nanoparticles (CTNs) as the second near-infrared (NIR-II) photothermal agents and GOx. In the tumor sites, GOx was gradually released from CAG to consume glucose for tumor starvation and aggravate acidity in tumor microenvironment that could turn on the NIR-II photothermal conversion property of CTNs. Meanwhile, the released GOx could suppress the expression of heat shock proteins to enable mild NIR-II PTT under 1,064 nm laser irradiation. As such, CAG mediated a combinational action of mild NIR-II PTT and starvation therapy, not only greatly inhibiting the growth of subcutaneously implanted tumors in a breast cancer murine model, but also completely preventing lung metastasis. This study thus provides an enzyme loaded hydrogel platform with a pH-sensitive photothermal effect for mild-temperature-mediated combinational cancer therapy.

Highlights

Photothermal therapy (PTT) that utilizes photoconversion to produce heat for tumor ablation has been explored as a non-invasive therapeutic strategy for cancer (Cheng et al, 2017; Jung et al, 2018; Zhao et al, 2018)
The therapeutic efficacy of mild PTT is often compromised by the upregulated expression of heat shock proteins (HSPs) that are associated with hyperthermia-induced cell damage (Ali et al, 2016; Wang et al, 2016; Wang et al, 2017)
The characteristic absorption of charge-transfer nanoparticles (CTNs) at different pH conditions was different and higher absorption in the NIR-II regions could be observed at acidic conditions (Figure 2A)

Summary

Introduction

Photothermal therapy (PTT) that utilizes photoconversion to produce heat for tumor ablation has been explored as a non-invasive therapeutic strategy for cancer (Cheng et al, 2017; Jung et al, 2018; Zhao et al, 2018). Most of existing mild PTT strategies are relied on the first nearinfrared (NIR) light (NIR-I, 650–950 nm) that shows too shallow tissue penetration depth to deliver sufficient heating to the internal regions of solid tumors (Gao et al, 2021). Compared to NIR-I light, the second near-infrared (NIR-II) light (1,000–1700 nm) has greatly improved penetrating capability in biological tissues (Li et al, 2021; Luo et al, 2021; Wang et al, 2021). In this regard, it is highly desired to develop mild NIR-II PTT for tumor ablation with high safety and efficacy

Methods

Results

Conclusion