Application of a Dual-Probe Coloading Nanodetection System in the Process Monitoring and Efficacy Assessment of Photodynamic Therapy: An In Vitro Study

Kai Dong; Hengyu Lei; Jian Kang; Xue Leng; Ruirui Ma; Danyang Wang; Qingyuan Zhou; Jie Yu; Tingli Lu; Jianfeng Xing

doi:10.1021/acsbiomaterials.2c01388

Application of a Dual-Probe Coloading Nanodetection System in the Process Monitoring and Efficacy Assessment of Photodynamic Therapy: An In Vitro Study

ACS Biomater Sci Eng. 2023 Feb 13;9(2):1089-1103. doi: 10.1021/acsbiomaterials.2c01388. Epub 2023 Jan 26.

Authors

Kai Dong¹, Hengyu Lei¹, Jian Kang², Xue Leng¹, Ruirui Ma¹, Danyang Wang¹, Qingyuan Zhou¹, Jie Yu¹, Tingli Lu², Jianfeng Xing¹

Affiliations

¹ School of Pharmacy, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an710061, Shaanxi, China.
² Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an710072, Shaanxi, China.

PMID: 36700559
DOI: 10.1021/acsbiomaterials.2c01388

Abstract

The oxygen-consuming property of photodynamic therapy (PDT) affects its effects and aggravates tumor hypoxia, thus upregulating the vascular endothelial growth factor (VEGF) to exacerbate tumor metastasis and lead to treatment failure. Therefore, it is necessary to monitor the dynamic changes in the factors related to PDT and tumor development trends in real time, thus helping to improve PDT efficiency. This study fabricated a fluorescent probe, TPE-2HPro, and a fluorescein-labeled aptamer probe, FAM-Aptamer_VEGF, to detect hydrogen peroxide (H₂O₂) and VEGF through the photoinduced electron-transfer effect and the specific affinity of the aptamer to VEGF, respectively. The two probes were loaded into the inner pores and absorbed on the surface of polydopamine coating-wrapped mesoporous silica nanoparticles (MSN@PDA) to construct the dual-probe-loaded system, MSN_TH@PDA_Apt, which was kept stable in fetal bovine serum (FBS) solution and achieved pH-responsive release behavior, thus helping to increase the accumulation of the two probes in tumor cells. The dichloroacetic acid-mediated in vitro antitumor tests showed that the changing trends of H₂O₂ and VEGF levels were consistent with the results of related mechanism studies and could be monitored by MSN_TH@PDA_Apt. The in vitro chlorin e6 (Ce6)-mediated PDT treatment demonstrated that when the illumination condition was 650 nm, 50 mW/cm² for 10 min, cells were more inclined to metastasis and invasion rather than death due to a substantial increase in VEGF expression at the low Ce6 concentrations. With the increase of the Ce6 concentration, the growth of the H₂O₂ level gradually exceeded that of VEGF, and the reactive oxygen species (ROS)-mediated cell death dominated when the Ce6 concentration was about 2 times its IC₅₀ values. Besides, hypoxia also affected the H₂O₂ and VEGF changes. These results demonstrated that MSN_TH@PDA_Apt could precisely monitor and assess the tumor development trends during PDT treatment, thus helping improve the treatment effect.

Keywords: aptamer; fluorescent probe; hydrogen peroxide; photodynamic therapy; vascular endothelial growth factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Hydrogen Peroxide / pharmacology
Nanoparticles*
Neoplasms* / drug therapy
Photochemotherapy* / methods
Vascular Endothelial Growth Factor A

Substances

Vascular Endothelial Growth Factor A
Hydrogen Peroxide