X‐Ray‐Responsive Zeolitic Imidazolate Framework‐Capped Nanotherapeutics for Cervical Cancer‐Targeting Radiosensitization

Abstract

Developing radiosensitizers based on the characteristics of the tumor microenvironment can improve the effectiveness and overcome the bottleneck of cervical cancer radiotherapy. Herein, an in situ synthesis strategy is demonstrated by using a highly bioactive zeolitic imidazolate framework to cap Mn 3 O 4 and folic acid as targeting molecules (FA-Mn 3 O 4 @ZIF-8) to achieve enhanced radiosensitization against cervical cancer. As expected, the ZIF-8 cap on the surface of Mn 3 O 4 responds more effectively to X-rays. Meanwhile, by facilitating the presence of oxygen vacancies and valence transition of manganese on the surface of Mn 3 O 4 , the ZIF-8 cap on Mn 3 O 4 can increase the catalytic capacity for hydrogen peroxide (H 2 O 2 ) and glutathione as well as produce more singlet oxygen under X-ray, alleviate hypoxia within the tumor microenvironment, and increase reactive oxygen species production. Moreover, FA-Mn 3 O 4 @ZIF-8 shows excellent radiotherapy-sensitizing properties in vitro and in vivo by promoting DNA damage and apoptosis. Collectively, this study suggests that designing and construction of X-ray responsive nanoradiosensitizers could be a good way for future clinical radiotherapy of malignant cervical cancer.

Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

“…), and other heavy elements (Hf, Ta, W, Bi, etc.). [ 239 ] Moreover, high‐Z elements can be integrated with semiconductor nanomaterials to further enhance the therapeutic effect of radiotherapy. [ 240 ] For instance, Wang et al.…”

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

“…Zhu and colleagues developed a radiosensitizer (FA-Mn 3 O 4 @ZIF-8) for efficient cervical cancer-targeting radiosensitization by combining zeolitic imidazolate framework (ZIF-8), Mn 3 O 4 , and folic acid (FA) as targeting molecules. [214] The FA-Mn 3 O 4 @ZIF-8 radiosensitizer demonstrated several responsive properties, making it highly effective in sensitizing RT for cervical cancer cells (Figure 12G). The presence of the ZIF-8 caps on Mn 3 O 4 increased the catalytic ability of H 2 O 2 and GSH, resulting in the generation of more singlet oxygen under X-ray irradiation.…”

Carbon dot-modified controllable drug delivery system for sonodynamic/chemotherapy of tumors

“…2 Currently, various combination therapies are available. According to different tumor microenvironments (TMEs), such as lower pH, 3 higher glutathione (GSH), [4][5][6] and excessive expression of folic acid receptors in cancer cells, 7,8 these characteristics have also been applied in combination therapy to achieve effects that cannot be achieved by a single treatment method. With the development of nanomedicine, multi-functional materials can be passively targeted into the tumor interior through the enhanced permeability and retention (EPR) effect so that targeted therapy can be performed at the tumor site.…”